Industrial Applications of Nanocrystals 9780128240243

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INDUSTRIAL APPLICATIONS OF NANOCRYSTALS

INDUSTRIAL APPLICATIONS OF NANOCRYSTALS Edited by

SHADPOUR MALLAKPOUR Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, Islamic Republic of Iran

CHAUDHERY MUSTANSAR HUSSAIN Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, United States

Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States Copyright © 2022 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-12-824024-3 For information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals Publisher: Matthew Deans Acquisitions Editor: Edward Payne Editorial Project Manager: John Leonard Production Project Manager: Prasanna Kalyanaraman Cover Designer: Miles Hitchen Typeset by TNQ Technologies

Dedication Dedication by C.M. Hussain I would like to dedicate this handbook to My beloved GOD “Meray Pyarey Allah (SWT)”

Dedication by S. Mallakpour I would like to dedicate this handbook to My wife Mina My son Iman My daughters Adeleh and Fereshteh My granddaughter Termeh

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Contents Contributors xiii About the editors xvii Preface xix Acknowledgments xxi

3. Bottom-up approaches 4. Combination approaches 5. Discussion 50 List of abbreviations 50 References 50

Section I

Suganthi Nachimuthu, S. Thangavel, and Karthik Kannan

1. 2. 3. 4. 5.

Introduction 53 Basic mechanism of green synthesis 54 Various methods for green synthesis 55 Factors affecting green synthesis 57 Application of green synthesized nanofunctionalized material 59 6. Conclusions and future outlook 66 References 66

1. Photonic crystal fibers for various sensing applications Murugan Senthil Mani Rajan

3

2. An overview of nanomaterial-enhanced miniaturized/microfluidic devices for electrochemical sensing

5. Biological and chemical impact of nanocellulose: current understanding Pragnesh N. Dave and Shalini Chaturvedi

Khairunnisa Amreen and Sanket Goel

1. History of nanocellulose 71 2. Nanocellulose: descriptions, use, and applications 71 3. Summary 76 References 77

1. Introduction 23 2. Synthesis of nanomaterials 24 3. Nanomaterial-based electrochemical sensing 25 4. Microfluidic/miniaturized device fabrication 26 5. Nanomaterial-enhanced microfluidic/miniaturized devices for electrochemical sensing 27 6. Conclusions and outlook 34 Acknowledgments 34 References 34

Section II Pharmaceutical industry 6. Recent trends in nanocrystals for pharmaceutical applications

3. Approaches for synthesis of nanocrytals: an overview

Pandey Annu and Ayushi Singhal

1. 2. 3. 4.

Gita Rani and Anu Bala

1. Introduction 43 2. Top-down approaches

48

4. Green synthesized nano-functionalized material

Nanomanufacturing: large-scale synthesis of nanocrystals

1. Introduction to photonic crystal fiber References 19

46

44

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Introduction 81 Production technology 83 Characteristics of drug nanocrystals Stabilization 87

85

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5. Fate in environment 6. Future prospects References 94

93

Section V

92

Drug delivery

7. Drug nanocrystals: emerging trends in pharmaceutical industries

10. Drug nanocrystals as drug delivery systems

S. Wazed Ali and Veerender Sharma

Shashi Kiran Misra and Kamla Pathak

1. Introduction 97 2. Different techniques for preparation of drug nanocrystals 98 3. Characterization and analysis of drug nanocrystal suspensions 102 4. Conclusions and future perspectives 113 References 113

1. Introduction 153 2. Challenges 172 3. Conclusion 173 References 173

11. Drug nanocrystals as nanocarrier-based drug delivery systems Sonika Arti, Monika Bharti, Vaneet Kumar, Saruchi, Vikrant Rehani, and Jitender Dhiman

Section III Biomedical industry 8. Colloidal as nanocrystals for biomedical applications Rakesh Kumar, Anika Parmar, Yanchen Dolma, Vaneet Kumar, Saruchi, and Naresh Kumar Dhiman

1. Introduction 119 2. Biomedical applications of colloidal nanocrystals 123 3. Conclusion 129 References 130

Section IV

1. 2. 3. 4.

Introduction 179 Role of nanoparticles in drug delivery 180 Nanocrystals as drug nanocarriers 181 Physical and chemical properties of nanocrystals 183 5. Method of preparation of drug nanosuspension 186 6. Applications of nanocrystals in drug delivery 192 7. Conclusion 198 References 199

12. Gold nanocarriers in tumor diagnosis, imaging, drug delivery, and therapy

Environmental industry

Vinitha Rani, Jayachandran Venkatesan, and Ashwini Prabhu

9. Environmental applications of MnO2 nanocrystals and their derivatives: from lab to real-time utilization

1. Introduction 205 2. Physicochemical and optical properties of gold nanocarriers 206 3. Synthesis and characterization of gold nanocarriers 207 4. Types of gold nanocarriers and their role in tumor diagnosis and imaging 208 5. Role of gold nanocarriers in drug delivery and targeted therapy 210 6. Mechanisms and signaling pathways involved in gold carrier-mediated drug delivery 211 7. Challenges in clinical translation of gold nanocarriers as efficient molecules in imaging and drug delivery 212 8. Conclusion and future perspectives 213 References 213

Shadpour Mallakpour, Mina Naghdi, and Chaudhery Mustansar Hussain

1. Introduction 135 2. Environmental applications 3. Toxicologic effects 146 4. Conclusion and perspective Acknowledgments 147 References 147

136 147

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CONTENTS

Section VI Catalysis 13. Zinc oxide-decorated graphene oxide nanocomposites for industrial volatile organic compound chemical sensor applications Santosh Singh Golia and Manju Arora

1. 2. 3. 4. 5.

Introduction 219 Air quality standards in India 221 Importance of problem 222 Synthesis and measurements 222 Characterization of ZnO nanoparticles, graphene oxide, and ZnOegraphene oxide nanocomposites 228 6. Volatile organic compound detection with ZnOe graphene oxide nanocomposite-based sensor 238 References 244

14. Shape-controlled synthesis of aqueousbased metallic nanocrystals and their catalytic applications Oladotun Paul Bolade, Ugochukwu Ewuzie, Chikaodili E. Chukwuneke, and Victoria Adams

1. Introduction 251 2. Understanding metal nanocrystal formation in solution 252 3. Monometallic nanocrystals 253 4. Binary nanocrystals 255 5. Advances in morphological characterization of green nanocrystals 258 6. Catalytic applications of nanocrystals 263 7. Challenges and future perspectives 267 8. Conclusion 267 References 268

15. Sustainable catalysis of nanocrystals: A green technology Rajmohan Rangasamy, Kannappan Lakshmi, and Karuppiah Muthu

1. Introduction 275 2. Coupling reactions 3. Oxidation reactions

277 286

4. Reduction/hydrogenation reaction 5. Nanocrystals in photocatalysis References 308

303

293

Section VII Antibacterial and antifungal coatings 16. Application of nanocrystals as antimicrobials N. Vigneshwaran, A. Arputharaj, N.M. Ashtaputre, and Charlene D’ Souza

1. Introduction 315 2. Nanomaterials and their mode of action 316 3. Nano-silver 318 4. Nano-copper 321 5. Metal oxide nanoparticles 323 6. Nanocarbon 325 7. Other nanomaterials 326 8. Conclusion 326 References 327

17. The antimicrobial activities of some selected polysaccharide nanocrystals and their hybrids: synthesis and applications Chandan Kumar Sahu, R. Rashmi, Jayanth S. Hampapura, and Ravi-Kumar Kadeppagari

1. Introduction 329 2. Biological nanocrystals and their antimicrobial activities 330 3. Inorganic nanocrystals and their antimicrobial activities 332 References 333

18. Applications of biogenic silver nanocrystals or nanoparticles as bactericide and fungicide Aruna Jyothi Kora

1. Introduction 335 2. Characterization techniques for silver nanoparticles 335 3. Biogenic synthesis of silver nanoparticles 336

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4. Applications of Ag nanoparticles as bactericide 339 5. Mechanism of bactericidal action of biogenic Ag nanoparticles 341 6. Applications of Ag nanoparticles as fungicides 346 7. Other antimicrobial applications of Ag nanoparticles 346 8. Conclusions 347 Acknowledgments 348 References 348

19. Crystalline nanomaterials for antimicrobial applications Deepika S. Brijpuriya, Dilip R. Peshwe, and Anupama Kumar

1. Introduction 353 2. Nanocrystals 354 3. Types of nanocrystals 355 4. Applications of nanocrystals 359 5. Toxicity of nanoparticles 360 6. Conclusions 360 References 361

Section VIII Electronics and energy industry 20. Applications of nanocrystals for antimicrobials Mithu Maiti Jana, Asim Kumar Jana, Rajeev Jindal, Deepika Gupta, Vaneet Kumar, and Saruchi

1. Introduction 367 2. Materials and methods 3. Results and discussion 4. Antibacterial studies 5. Conclusions 395 References 395 Further reading 397

374 376 390

21. Selected copper-based nanocomposite catalysts for CO2 reduction Srijita Basumallick

1. Introduction 401 2. Role of different components of composite catalysts 402 3. Preparation of composite catalyst 403 4. Characterization of nanocomposites 404

5. Applications of the composites 6. Conclusions 406 Acknowledgments 406 References 407

404

22. Nanocrystals for electrochemical energy storage devices S. Imran Hussain, S. Karthick, A. Arulraj, and R.V. Mangalaraja

1. Introduction 409 2. Perovskite structured nanocrystals 3. Organic nanocrystals 413 4. Chalcogenide-based nanocrystals 5. Summary 422 Acknowledgments 422 References 422

411 418

23. Nanoscience and its role in the future of solar stills Ahmed Kadhim Hussein, Lioua Kolsi, Mohammed El Hadi Attia, Obai Younis, Uddhaba Biswal, Hafiz Muhammad Ali, Bagh Ali, Mehran Hashemian, B. Mallikarjuna, and Rasoul Nikbakhti

List of abbreviations 428 1. Introduction 428 2. Distillation process: a general concept 3. Distillation techniques 429 4. Solar still 429 5. Some types of solar stills 431 6. Advantages of nanofluid in solar stills 7. Using of the nanofluid in the solar stills 434 8. Conclusions 436 References 436 Further reading 440

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Section IX Conclusion 24. Green carbon quantum dots: eco-friendly and sustainable synthetic approaches to nanocrystals Shikha Gulati, Sanjay Kumar, Parinita Singh, Ayush Mongia, and Anchita Diwan

1. Introduction 443 2. General synthetic approaches to nanocrystalline carbon quantum dots 448 3. Surface modifications 451

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4. Need for green method to synthesize carbon quantum dots 452 5. Green chemistry principles 453 6. Eco-friendly and sustainable synthetic approaches of green carbon quantum dots 455 7. Biological and biotechnological applications of carbon quantum dots 455 8. Conclusion and future perspectives 459 References 460 Further reading 466

25. Metal nanoparticles for catalytic hydrogenation reactions Shilpa Dabas, Parth Patel, Manas Barik, Saravanan Subramanian, and K.S. Prakash

1. Introduction 467 2. Catalytic applications of nanocrystals 3. Conclusions 480 Acknowledgments 480 References 480

Index

483

470

Contributors Victoria Adams Department of Petroleum Chemistry, School of Arts and Sciences, American University of Nigeria, Yola, Adamawa, Nigeria S. Wazed Ali Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India Hafiz Muhammad Ali Mechanical Engineering Department, King Fahd University of Petroleum and Minerals, Dhahran, Eastern Province, Saudi Arabia; Interdisciplinary Research Center for Renewable Energy and Power Systems (IRC-REPS), King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia Bagh Ali Faculty of Computer Science and Information Technology, Superior University, Lahore, Pakistan Khairunnisa Amreen MEMS, Microfluidics and Nanoelectronics Lab, Department of Electrical and Electronics Engineering, Birla Institute of Technology and Science, Hyderabad, Telangana, India Pandey Annu School of Studies in Environmental Chemistry, Jiwaji University, Gwalior, Madhya Pradesh, India; Department of Chemistry, Chandigarh University, Mohali, Punjab, India Manju Arora CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi, India A.

Arputharaj ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India

Sonika Arti Department of Chemistry, DAV College, Jalandhar, Punjab, India A. Arulraj Advanced Ceramics and Nanotechnology Laboratory, Department of Materials Engineering, University of Concepcion, Concepcion, Bio Bio, Chile

N.M. Ashtaputre ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India Anu Bala Department of Chemistry, Chaudhary Devi Lal University, Sirsa, Haryana, India Manas Barik Inorganic Materials and Catalysis Division, CSIReCentral Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India Srijita Basumallick Asutosh College Under Calcutta University, Kolkata, West Bengal, India Monika Bharti Department of Chemistry, Himachal Pradesh University, Shimla, India Uddhaba Biswal Department of Mathematics, National Institute of Technology Rourkela, Rourkela, Odisha, India Oladotun Paul Bolade Department of Petroleum Chemistry, School of Arts and Sciences, American University of Nigeria, Yola, Adamawa, Nigeria Deepika S. Brijpuriya Postgraduate Department of Chemistry, Santaji Mahavidyalaya, Nagpur, Maharashtra, India Shalini Chaturvedi Department of Chemistry, Silver Oak Institute of Science, Silver Oak University, Ahmedabad, Gujarat, India Chikaodili E. Chukwuneke Department of Petroleum Chemistry, School of Arts and Sciences, American University of Nigeria, Yola, Adamawa, Nigeria Shilpa Dabas Inorganic Materials and Catalysis Division, CSIReCentral Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India

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CONTRIBUTORS

Pragnesh N. Dave Department of Chemistry, Sardar Patel University, Anand, Gujarat, India

Jersey Institute of Technology, Newark, NJ, United States

Naresh Kumar Dhiman Department of Physics, Government Degree College, Sujanpur Tihra, Himachal Pradesh, India

Ahmed Kadhim Hussein College of Engineering, Mechanical Engineering Department, University of Babylon, Babylon, Hilla, Iraq

Jitender Dhiman Biotechnology Division, Central Pulp and Paper Research Institute, Saharanpur, India

Mithu Maiti Jana Department of Physical Sciences, Sant Baba Bagh Singh University, Jalandhar, Punjab, India

Anchita Diwan Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India

Asim Kumar Jana Department of Biotechnology, Dr. B.R. Ambedkar National Institute of Technology, Jalandhar, Punjab, India

Yanchen Dolma Department of Chemistry, MCM DAV College, Kangra, Himachal Pradesh, India

Rajeev Jindal Department of Chemistry, Dr. B.R. Ambedkar National Institute of Technology, Jalandhar, Punjab, India

Mohammed El Hadi Attia Physics Department, Faculty of Exact Sciences, University of El Oued, El Oued, Algeria

Ravi-Kumar Kadeppagari Centre for Incubation, Innovation, Research, and Consultancy, Department of Food Technology, Jyothy Institute of Technology, Tataguni, Bengaluru, Karnataka, India

Ugochukwu Ewuzie Analytical Unit, Department of Pure and Industrial Chemistry, Abia State University, Uturu, Abia, Nigeria Sanket Goel MEMS, Microfluidics and Nanoelectronics Lab, Department of Electrical and Electronics Engineering, Birla Institute of Technology and Science, Hyderabad, Telangana, India Santosh Singh Golia CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi, India Shikha Gulati Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India Deepika Gupta Department of Chemistry, Dr. B.R. Ambedkar National Institute of Technology, Jalandhar, Punjab, India Jayanth S. Hampapura Department of Microbiology, Yuvaraja’s College, Mysuru, Karnataka, India Mehran Hashemian Department of Mechanical Engineering, Faculty of Engineering, Urmia University, Urmia, West Azerbaijan, Iran S. Imran Hussain Centre for Micro Nano Design and Fabrication, Department of Electronics and Communication Engineering, Saveetha Engineering College, Thandalam, Chennai, Tamil Nadu, India Chaudhery Mustansar Hussain Department of Chemistry and Environmental Science, New

Karthik Kannan School of Advanced Materials Science and Engineering, Kumoh National Institute of Technology, Gyeongbuk, Republic of Korea S.

Karthick Department of Physics, Muthayammal Engineering College, Namakkal, Tamil Nadu, India

Lioua Kolsi College of Engineering, Mechanical Engineering Department, Ha’il University, Ha’il, Ha’il Province, Saudi Arabia; Research Laboratory of Metrology and Energy Systems, National Engineering School, University of Monastir, Monastir, Monastir, Tunisia Aruna Jyothi Kora National Centre for Compositional Characterisation of Materials, Bhabha Atomic Research Centre, ECIL PO, Hyderabad, Telangana, India; Homi Bhabha National Institute, Mumbai, Maharashtra, India Rakesh Kumar Department of Chemistry, MCM DAV College, Kangra, Himachal Pradesh, India Sanjay Kumar Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India Anupama Kumar Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, India

CONTRIBUTORS

xv

Vaneet Kumar Department of Applied Sciences, CTIEMT, CT Group of Institutions, Jalandhar, Punjab, India

Anika Parmar Department of Sciences, Government Degree College, Khundian, Himachal Pradesh, India

Kannappan Lakshmi Department of Chemistry, Guru Nanak College (Autonomous), Velachery, Chennai, Tamil Nadu, India

Parth Patel Inorganic Materials and Catalysis Division, CSIReCentral Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, India; Charotar University of Science and Technology, Anand, Gujarat, India

Shadpour Mallakpour Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, Islamic Republic of Iran B. Mallikarjuna Department of Mathematics, BMS College of Engineering, Bangalore, Karnataka, India R.V. Mangalaraja Advanced Ceramics and Nanotechnology Laboratory, Department of Materials Engineering, University of Concepcion, Concepcion, Bio Bio, Chile; Technological Development Unit (UDT), University of Concepcion, Coronel, Bio Bio, Chile

Kamla Pathak Faculty of Pharmacy, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh, India Dilip R. Peshwe Department of Metallurgical and Materials Engineering, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, India Ashwini Prabhu Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India

Murugan Senthil Mani Rajan Department of Physics, Anna University, University College of Engineering, Ramanathapuram, Tamil Nadu, India

K.S. Prakash Department of Chemistry, Bharathidasan Government College for Women (Autonomous) (Affiliated to Pondicherry University, Pondicherry), Muthialpet, Puducherry UT, India

Shashi Kiran Misra University Institute of Pharmacy, CSJM University, Kanpur, Uttar Pradesh, India

Rajmohan Rangasamy Department of Chemistry, Guru Nanak College (Autonomous), Velachery, Chennai, Tamil Nadu, India

Ayush Mongia Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India

Gita Rani Department of Chemistry, Chaudhary Devi Lal University, Sirsa, Haryana, India

Karuppiah Muthu Department of Chemistry, Manonmaniam Sundaranar University, Abishekapatti, Tirunelveli, Tamil Nadu, India Suganthi Nachimuthu Department of Physics, Government Arts College (Affiliated to Bharathidasan University), Kulithalai, Karur, Tamilnadu, India Mina Naghdi Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, Islamic Republic of Iran Rasoul Nikbakhti School of Engineering, College of Sciences and Engineering, University of Tasmania, Hobart, TAS, Australia

Vinitha Rani Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India R. Rashmi Centre for Incubation, Innovation, Research, and Consultancy, Department of Food Technology, Jyothy Institute of Technology, Tataguni, Bengaluru, Karnataka, India Vikrant Rehani Department of Applied Sciences, CTIEMT, CT Group of Institutions, Jalandhar, Punjab, India Chandan Kumar Sahu Centre for Incubation, Innovation, Research, and Consultancy, Department of Food Technology, Jyothy Institute of Technology, Tataguni, Bengaluru, Karnataka, India

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CONTRIBUTORS

Saruchi Department of Biotechnology, CTIPS, CT Group of Institutions, Jalandhar, Punjab, India

Innovative Research, Ghaziabad, Uttar Pradesh, India

Veerender Sharma Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India

S. Thangavel PG and Research Department of Physics, Jairams Arts and Science College (Affiliated to Bharathidasan University), Karur, Tamilnadu, India

Parinita Singh Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India Ayushi Singhal CSIReAdvanced Materials and Process Research Institute, Bhopal, Madhya Pradesh, India Charlene D’ Souza ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India Saravanan Subramanian Inorganic Materials and Catalysis Division, CSIReCentral Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, India; Academy of Scientific and

Jayachandran Venkatesan Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India N. Vigneshwaran ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India Obai Younis Department of Mechanical Engineering, College of Engineering at Wadi Addwaser, Prince Sattam Bin Abdulaziz University, Wadi Addwaser, Saudi Arabia; Department of Mechanical Engineering, Faculty of Engineering, University of Khartoum, Khartoum, Sudan

About the editors Chaudhery Mustansar Hussain, PhD, is an adjunct professor and director of laboratories in the Department of Chemistry and Environmental Science at the New Jersey Institute of Technology, Newark, New Jersey. His research focuses on the applications of nanotechnology and advanced materials, environmental management, analytical chemistry, smart materials and technologies, and other various industries. Dr. Hussain is the author of numerous papers in peer-reviewed journals and is a prolific author and editor of around 100 books, including scientific monographs and handbooks in his research areas. He has published with Elsevier, American Chemical Society, Royal Society of Chemistry, Springer, John Wiley & Sons, and CRC Press. Professor Shadpour Mallakpour, an organic polymer chemist, graduated from the Chemistry Department at the University of Florida (UF), Gainesville, Florida, in 1984. He spent 2 years as postdoctoral student at UF. He joined the Department of Chemistry, Isfahan University of Technology (IUT), Iran, in 1986. He has held several positions, such as chairman of the Department of Chemistry and deputy of research, Department of Chemistry at IUT. From 1994 to 1995, he worked as a visiting professor at the University of Mainz, Germany, and from 2003 to 2004 as a visiting professor at Virginia Tech, Blacksburg, Virginia. He has published more than 900 journal papers and book chapters and more than 440 conference papers, and has received more than 40 awards. The most important to him was awarded for the selection of First Laureate on Fundamental Research at the 21st Khwarizmi International Awards in 2008. He is listed as one of the Top 1% Scientists in Chemistry in ISI Essential Science Indicators Since 2003. He was selected as an academic guest of the 59th Meeting of Nobel Prize Winners in Chemistry, 2009, at Lindau, Germany. He has presented many lectures as an invited or keynote speaker in different national and international conferences and universities. He has been a member of organizing and scientific committees for many national and international conferences. He has also been the chairperson of many national and international meetings. In recent years, he has focused on the preparation and characterization of polymers containing chiral amino acid

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ABOUT THE EDITORS

moieties under green conditions using ionic liquids and microwave irradiation as a new technology, bringing these aspects towards nanotechnology for the preparation of novel chiral bionanocomposite polymers as well as polymer nanocomposites for hazardous material removal technologies. Prof. Shadpour Mallakpour Department of Chemistry Isfahan University of Technology, Isfahan 84156-83111, I.R. Iran. [email protected]

Preface To capture a comprehensive impression of industrial applications of NCs and provide readers with a coherent representation, the book is divided into several sections, each of which is composed of different chapters. Section 1 is about nanomanufacturing and contains chapters on photonic crystal fibers for various sensing applications, approaches to synthesis, the green synthesis of NCs, and the biological and chemical impacts of nanocellulose on synthesis. Section 2 debates the applications of NCs in the pharmaceutical industry in terms of emerging trends. Sections 3 and 4 elaborate on applications of NCs in the biomedical and environmental industries. Section 5 presents NCs as drug delivery systems, nanocarrier drug delivery systems, and gold nanocarriers for tumor diagnosis, imaging, drug delivery, and therapy. Section 6 is an overview of applications of NCs in the catalysis industry. Antibacterial and antifungal coatings made with NCs are the topic of Section 7. The last section discusses NCs for electrochemical energy storage devices and their role in the future of solar stills. The conclusion describes emerging applications of NCs. Overall, this book is intended as a reference guidebook for experts, researchers, and scientists who are searching for modern developments in microbial nanotechnology. The editor and authors are well-known researchers, scientists, and specialists from various universities and industries. On behalf of Elsevier, I am very delighted with all authors for their outstanding and

Nanocrystals (NCs) are a key element in nanoscale devices, whose design and function can be tuned by tailoring the fundamental chemical and physical properties of integrated nano-objects. NCs have interesting optical, electrical, and chemical properties that are not found in their bulk counterparts. Quantum-confinement effects mean that small changes in their size and shape can have significant effects on the physical properties and spectroscopy of NCs. Size and shape control has been a hot topic during developments in the field of NC synthesis. Success in colloidal chemistry has produced a great variety of NCs with controlled sizes and shapes, which could be used as functional materials for numerous applications. As a result, NCs are predicted to be a main driver of technology and business and to hold the promise of highperformance materials that will significantly affect all aspects of society. Likewise, NCs are taking part in the development and innovation of different manufacturing sectors. Despite their participation in modern development, there are some hindrances to the superior impact of NCs in manuacturing. The aim of this book is to reveal advances in various industrial sectors because of NCs. Enhancements in industrial techniques and processes owing to NCs can overtake procedures that are already in use, and can deliver exciting consumer products to society. Special attention is paid to approaches that tend toward green and sustainable industrial practices.

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PREFACE

enthusiastic hard work in the making of this book. Very special acknowledgments to Edward Payne (acquisition editor), John Leonard (editorial project manager), and Prasanna Kalyanaraman (production manager) at Elsevier for their devoted support and help during this project. In the end, I

offer my sincere thanks to Elsevier for publishing the book. Shadpour Mallakpour, Ph.D. Chaudhery Mustansar Hussain, Ph.D. (Editors)

Acknowledgments We would like to acknowledge Chaudhery Ghazanfar Hussain for his dedicated support during the compilation of this book. We also would like to thank Dr. Vajiha

Behranvand, Dr. Farbod Tabesh, Miss Fariba Sirous, and Miss Elham Azadi for their special support during the preparation of this book.

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Nanomanufacturing: large-scale synthesis of nanocrystals

C H A P T E R

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Photonic crystal fibers for various sensing applications Murugan Senthil Mani Rajan Department of Physics, Anna University, University College of Engineering, Ramanathapuram, Tamil Nadu, India

1. Introduction to photonic crystal fiber In a periodically structured optical medium, the property of light was an attractive area of research in the 20th century. After the invention of photonic crystals, a novel light guiding mechanism became possible that was not achievable in conventional optical fibers owing to their inherent limits. Generally, these crystals are arranged periodically with dielectric structures of low and high dielectric constants. Also, these structures contain a photonic bandgap that prohibits the propagation of light for a certain wavelength regime. Photonic crystal fibers (PCFs) have good features such as geometry control, a high core index of refraction, efficient coupling, and a high numerical aperture (NA). PCFs are a generation of optical fiber that attracts considerable attention both theoretically and experimentally [1e4]. Conventional fiber fabrication is unsuitable because of the large refractive index contrast required for PCF. A cross-section of fabricated PCF can be viewed and examined by an optical microscope to measure fiber parameters, such as the air hole diameter, core diameter, and pitch. This kind of optical fiber is a promising candidate for many potential applications such as nonlinear fiber optics, fiber lasers, optical sensors, and plasmonics because the fabrication technology allows for better tunability in the design of fibers. Researchers across the world have put tremendous effort into developing fibers with photonic materials in which the electromagnetic wave can be manipulated. Consequently, PCFs were developed and offered a new direction in photonics technology [5]. These fibers were developed by Russel and called microstructured fibers or holey fibers [6]. Conventional optical fibers have two main layers, core and cladding, which have a higher and lower refractive index, respectively, whereas PCF consists of photonic crystal cladding, which is a periodic array of air holes with a silica background. Also, in conventional optical fibers, light is propagated by the principle of total internal reflection (TIR).

Industrial Applications of Nanocrystals https://doi.org/10.1016/B978-0-12-824024-3.00017-8

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© 2022 Elsevier Inc. All rights reserved.

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1. Photonic crystal fibers for various sensing applications

Compared with conventional optical fibers, PCF offers some conceptual difficulties in real applications owing to its complex structure and methodology for light guidance [6]. In modern fiber optic technology, conventional optical fibers exhibit poor performance owing to limitations such as an endlessly single mode operation with a large wavelength range, an extremely large or small core area with a single mode operation, anomalous group velocity dispersion (GVD) at visible and near infrared (NIR) wavelengths, a large mode area, high birefringence, controllable dispersion in a desirable way, and high optical nonlinearity, which cannot be achieved in conventional optical fibers. On the other hand, the arrangement of air holes with a controllable air hole size and pitch value (distance between holes) offers possibilities for designing PCFs in which the optical properties are excellent and can be controlled. This design flexibility is the most important feature of a PCF. It offers desirable optical properties for various applications. Hence, investigation into PCF characteristics and applications is an attractive research area in the modern world of technology [7].

1.1 Types of photonic crystal fibers Generally, PCF are classified into two categories based on their structure and guidance mechanism: (i) PCF with a solid core (ii) PCF with a hollow core In solid core PCF, the central core region is surrounded by a periodic array of numerous air holes embedded in silica material. On the other hand, in hollow core PCF, there is a periodic arrangement of photonic crystals acting as cladding whereas the large central core is hollow.

1.2 Guiding mechanism In index guiding PCF, light is propagated by the principle of TIR as in conventional fibers. For example, in telecom applications, light rays are propagated in the fiber with the principle of TIR. In the case of photonic bandgap fibers or hollow fibers, light is confined with the effect of the photonic bandgap and a special kind of fiber is fabricated [1]. This photonic bandgap effect is similar to the Bragg effect. In hollow core PCF, the core material is filled with air whose refractive index is less than the effective refractive index of the cladding region. Hence, the TIR process is impossible in this structure, and the wave guidance nature wholly depends on the photonic bandgap of the photonic crystal cladding. In such fibers, the photonic bandgap does not allows certain wavelength regimes in which Maxwell’s equations do not have solutions. However, by adjusting the periodicity of the photonic crystal, one can select the wavelength range where propagation can be prohibited. In fiber optics, it is necessary to propagate light within the core region with propagation constant b along the fiber’s axis. To prevent the propagation of light in the cladding region, incident light must be confined to the central core region. According to the propagation constant, the mode distributed in a fiber reveals the variations of amplitude and phase along the

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direction of propagation in a guided medium. The refractive index of the medium and optical frequency of the incident light are responsible for the field distribution.

1.3 Optical properties of photonic crystal fiber By tailoring the air hole diameter (d) and pitch (Ʌ) value of the PCF structure, one can manipulate the optical properties of the waveguide, which are not achievable in conventional optical fibers. These two parameters are offer additional degrees of freedom and can easily be tailored to provide the desired dispersion for numerous applications in the area of photonics. Also, the ratio of these two parameters (d/L) has a vital role in determining the characteristics of propagation. In PCFs, nonlinear effects are significantly enhanced even when the fiber length is within a few centimeters. Also, dispersion properties are controllable and engineered to a desirable value for advanced optical communication and supercontinuum generation. Because of structurally dependent dispersion and nonlinear properties, PCFs have received major attention for some potential applications in the world of photonics. 1.3.1 Endlessly single mode operation PCFs show endlessly single mode behavior for a wide range of wavelength, which is not observable in standard or conventional fibers [8]. According to this phenomenon, PCF propagate only a fundamental mode, and even at a low wavelength range, higher-order modes are strictly prohibited. Mostly single mode PCFs have a relatively small d/L ratio with a large core area. At first, endlessly single mode fibers were reported with a single mode operation for a wide range of wavelengths (480e1550 nm). A numerical study on PCFs implies that the fiber never supports higher order modes with the condition d/L < 0.43 [9]. Thus, by fixing the air filling fraction, we can get the single mode operation for a wide range of wavelengths. The cladding index of PCF is mainly a function of the wavelength when the size of the microstructure is of the same order as that of the wavelength. For the cladding region, the higher order mode remains cut off at a wide range of wavelengths and supports the endlessly single mode operation. Practically, to achieve single mode operation, the design parameters must satisfy the conditions of a core with a radius of L/O3 and a diameter-to-pitch (d/L) ratio less than 0.43 (i.e., d/L < 0.43) [10]; then, that particular microstructured optical fibers (MOF) will hold the endlessly single mode phenomenon. 1.3.2 Effective refractive index The effective index (neff) of the cladding is not a constant and varies with respect to the wavelength. To study the optical properties of PCFs, effective indices of guided modes are essential [3]. By properly tuning the air filling ratio (d/L), an effective index can be attained with desirable values for various applications and a wide range of NAs (0.5), which strongly depend on the wavelength. neff can be calculated by means of the mode solver in COMSOL Multiphysics. The index difference in PCFs helps to guide the light within the core region by means of Modified-TIR. Tailoring the air hole diameter (d) and pitch (L) in a PCF offers additional degrees of freedom for some exclusive possibilities to manipulate light, which are not possible in standard optical fibers.

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1. Photonic crystal fibers for various sensing applications

1.3.3 Dispersion In an optical medium, when an optical pulse is transmitted, different frequency components will travel with different velocities that exhibit the frequency-dependent refractive index of the medium [11]. This process is known as the GVD. In the concept of optical fibers, there are two different regimes for dispersion: normal and anomalous. In the anomalous dispersion regime, higher-frequency components travel faster than lower-frequency components, and vice versa in the case of the normal dispersion regime. Generally, many types of dispersion contribute to the total dispersion of the optical fiber medium. However, two dispersions are most important: material and waveguide dispersion. Material dispersion is the most notable because of the wavelength dependence refractive index whereas waveguide dispersion takes place owing to changes in field distribution with the wavelength. The waveguide dispersion is mainly determined by differences between the core and the effective cladding index of the PCF. In PCFs, one can tailor the dispersion profile by properly tuning the refractive index difference. Broadening an input optical pulse mainly takes place as the result of different frequency components taking different times along the propagation. However, because any source of light would have a certain spectral width and each spectral component of it generally travels with a different group velocity, we would always have dispersion. This is referred to as material dispersion; it has an important role in designing a fiber opticebased communication system. GVD is used to determine the amount of pulse spreading during light propagation in the optical medium. The optical pulse is propagated through the medium in the form of a monochromatic wave packet with group velocity vg. The greater refractive index difference between the silica solid core and air cladding can be achieved by tuning the air hole size and crystal patterns, which offer a variety of dispersion characteristics for PCFs. Thus, dispersion parameter (D) for PCFs can be described and computed from the real part of neff [12]:
 l d2 Re neff D¼  ps=km=nm (1.1) c dl2 where c is the velocity of light in vacuum, l is the operating wavelength, and neff is the effective index of the guided mode. PCF is a promising candidate for obtaining novel dispersion properties. In the case of conventional standard fiber, 1.27 mm is a zero dispersion wavelength whereas the waveguide contribution to dispersion can be tailored to any desired wavelength for a wide range of PCFs by suitably changing the geometrics of the air holes. 1.3.4 Birefringence Birefringence is an important property of PCFs. It is possible to enhance the birefringence manifold for some potential applications [13]. In strong birefringent fibers, two orthogonally polarized modes are propagated in a single mode fiber that propagate at different rates. By changing the geometry of the air holes in a PCF, it is possible to induce birefringence up to many orders, which can exceed the birefringence of conventional fiber. Furthermore, birefringence is highly insensitive to temperature in a PCF, which is

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a peculiar property unlike polarization maintaining fibers such as bowtie and elliptical core. On the other hand, conventional polarization maintaining fibers generally contain two different glasses with different thermal expansion coefficients. Birefringence can be calculated by the expression [14]: y

B ¼ nxeff  neff

(1.2)

y

where nxeff and neff respectively denote the refractive indexes of x and y polarizations. High birefringence PCFs receive major attention in the fields of fiber-optic communication system, fiber lasers, and fiber sensors. In addition, negative or flattened dispersion can be obtained, which makes them suitable for various applications such as dispersion controllers, dispersion compensators, and nonlinear optical devices. 1.3.5 Large mode area PCFs with the property of a large mode area (LMA) are important for generating high power optical lasers [15]. In particular, nonlinear effects can be suppressed, which are caused by the fiber material. These fibers can be achieved by increasing the fiber core size and decreasing the NA. However, index guiding PCFs offer an alternative way to achieve LMAs. The most notable property of PCFs is the single mode operation at a wide range of wavelengths. LMA PCFs have a small effective index difference between the core and cladding, which leads to sensitive macro- and microbending. Because of the additional design flexibility, PCFs provide enhanced effective mode areas for some potential applications. The combined properties of single mode operation and large mode are important for the transmission of high-power optical laser beams. By tailoring the hole size with the proper arrangement, effective refractive indices can be attained with desirable values. 1.3.6 High nonlinearity The development of PCFs with high nonlinearity has opened a window for many nonlinear applications such as wavelength conversion and nonlinear switching because of their ultrahigh nonlinear value. Highly nonlinear PCFs have many potential applications in various interesting fields including optical coherence tomography [16], spectroscopy [17], and supercontinuum generation [18]. Moreover, highly nonlinear PCFs need low threshold input power to generate a broadband supercontinuum. The nonlinearity of PCFs strongly depends on the effective mode area [19]: g¼

2pn2 1 1 W m lAeff

(1.3)

where n2 is the nonlinear coefficient of the refractive index and Aeff is the effective area of the fundamental mode. From this expression, one can infer that high nonlinearity can be achieved for a small value of the effective area. Nonlinearity is enhanced for various nonlinear optical materials and some novel PCF structures [20]. Because of the tight confinement of optical modes, silica PCF offers high nonlinearity.

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1. Photonic crystal fibers for various sensing applications

1.4 Applications As a result of the development of optical fiber technology, PCF fabrication has become simple. Hence, plenty of PCF novel structures are proposed that embrace octagonal [21], honeycomb cladding [22], spiral [23], pentagonal [24], and D-shaped [25] structures. These are investigated owing to their various light guiding properties, such as a large effective area (Aeff) [26], ultraflat dispersion [27], beam divergence [28], and large NA [29] for various PCF structures. From the various investigations, PCFs are promising candidates for some applications such as nonlinear fiber optics [30], Raman spectroscopy [31], supercontinuum generation [32], fluorescence imaging [33], and sensing [34] areas. Physical and biosensors are a major classification of PCF-based sensors. Moreover, nonlinearity is an important property of PCFs. Cross-phase modulation, optimum self-phase-modulation, and the Brillouin scattering coefficient of the system use nonlinear fiber [35].

1.5 High birefringence photonic crystal fibers for pressure sensor Consider the highly birefringent PCF (HB-PCF) for hydrostatic pressure sensing applications. The proposed PCF is considered for achieving birefringence and maximum birefringence attained on the order of 1.2  102 at the particular wavelength of 1.55 mm. The prime objective of the designed pressure sensor is based on the selective material in which external stress is applied with help of stress-optic coefficients. When hydrostatic pressure is applied on the sensor, refractive index is changed in the solid core where light propagated and corresponding wavelength shifting in the transmission spectrum. The sensitivity of sensor is calculated as 31.2 pm/MPa at a pitch constant of 2 mm. 1.5.1 Proposed photonic crystal fiber structure The physical structure of the HB-PCF is portrayed in Fig. 1.1. It has seven ring patterns of air holes which make up the cladding region and two elliptical holes are stressed in the core region to create the elliptical core shape. To achieve higher birefringence, the dimensions of elliptical hole are fixed as da ¼ 8  L and db ¼ 0.5  L. The outer cladding perfectly matched layer (PML) region is considered for d ¼ 0.95  L, where L represents the pitch constant of a typical air hole and is chosen to be 1.9 mm. To form a solid elliptical core, 21 air holes are removed at the nearest inner ring region and extend the two air holes in the horizontal and vertical directions to make them into an elliptical hole. The presence of the elliptical hole gives the elliptical mode field distributions horizontal and vertical directions respectively known as X- and Y-polarizations. The basic optical properties of HB-PCF are successfully studied by finite-difference time-domain (FDTD) method, which is given in detail by Yang et al. [36]. The design structure also shows some remarkable properties such as high birefringence at 102, endlessly single mode fiber, a small walk-off effect, and anomalous dispersion over a wide range of wavelengths. The core medium is made of silica whose refractive index is 1.45, and the cladding holes are filled with air. The mode propagation and its field strength are shown in Fig. 1.2. The fiber has two orthonormal polarized modes, as previously stated. In general, the PCF, which has larger birefringence, is used for pressure sensing applications [37]. The sensitivity of the proposed design is

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FIGURE 1.1 Cross-section of highly birefringent photonic crystal fiber pressure sensor.

FIGURE 1.2

Elliptical shape mode propagation of highly birefringent photonic crystal fiber.

also tuned under the proper optimization process. Pressure on the surface of the microstructure optical fiber is applied by the proper placement of fiber with reference to the axis of the transverse load. While applying the load on the fiber surface, stress is induced in the outer boundary and air holes are started for cladding deformation. Deformation leads to core stress in single mode propagation and result is a phase changing mechanism with the effect of applied pressure. Sensitivity in the pm scale is then reported to prove its higher sensing principle.

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1. Photonic crystal fibers for various sensing applications

1.5.2 Fiber parameters As auxiliary parameters for sensing calculations, parameters such as the coupling length, transmission spectrum, and wavelength shift are calculated to explore the sensing performance. First, the effect of birefringence is studied by breaking the symmetry pattern of the core region. Another method [38e40] to break the symmetry is to introduce the asymmetric elliptical hole in the near core region. In this design, the symmetry properties are broken by introducing the elliptical hole at the innermost region of the core region; hence, two kinds of orthonormal polarized modes can be generated. In this way to break asymmetry, it can easily be adjusted by varying the dimensions of the air holes, which results in optimized higher birefringence values [36]. Phase and group modal birefringence are usually used to describe the effect of birefringence (Eq. 1.4): B ¼ Dn ¼ jne  n0 j

(1.4)

The property of birefringence is obtained by determining the difference between two refractive indexes of X- and Y-polarized modes. The phase modal birefringence is calculated for the wavelength region from 0.6 to 2 mm for unloaded fiber at asymmetric conditions, as shown in Fig. 1.3. The plot gives the variations in birefringence with respect to different air hole radii and with the functions of the major and minor axes of the innermost two elliptical air holes. The birefringence increases with an increase in wavelength. During mode propagation, the field is seriously affected by asymmetry and splits the two polarizations into the horizontal and vertical directions. The effects are described in terms of birefringence, with a maximum value of 1.2  102 at a wavelength of 2 mm. The radiuses of air holes are adjusted to 1.5 mm. In the same way, the enhancement of birefringence is still relevant through the process of the proper optimization of the radius of air holes and the major and minor axes of the innermost elliptical air hole. Fig. 1.3 also shows that variations in birefringence depend on the pitch FIGURE 1.3 Effect of birefringence with function of wavelength.

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size of air holes. For example, the pitch constant of L ¼ 1.5 mm offers low birefringence for the given wavelength region, whereas the pitch constant of L ¼ 1.1 mm offers higher birefringence at the particular wavelength region. During the reduced pitch size, the asymmetry of elliptical core region is increased and the corresponding birefringence is improved. Because the wavelength bands covers the communications range, the structure is promising for telecom applications. When light propagates along the core region, the odd and even mode of the same polarizations will be coupled. The measuring factor for the coupling range is calculated from Eq. (1.5), which gives information about the maximum coupling length between the even and odd modes [36]: Lx;y ðlÞ ¼

l 2jne  n0 j

(1.5)

The coupling length is decreased with the function of wavelength, as clearly shown in Eq. (1.2). Hence, the degree of variation of birefringence is also correlated with the coupling length parameter. The calculated results are plotted as shown in Fig. 1.4. The calculation of coupling length is studied from the birefringence. Fig. 1.4 illustrates the maximum birefringence of 102 at L ¼ 1.1 mm. At these conditions, the design is intended for various pressure applications and directly affects the innermost elliptical holes near the core region. When increasing the value of pressure, the elliptical hole deformed significantly and coupling strength of even and odd modes are easily obtained with different applied pressure for given wavelength range region. This design is able to tolerate a pressure of up to 900 MPa and also accepts experimental cases from the previous literature. A minimum pressure of 100 MPa to a maximum of 900 MPa is applied on the surface of PCF boundaries. The strength of the coupling length is improved for a higher amount of pressure and decreases for the incremental wavelength region. In this proposed design, the introduced elliptical air hole near the core region FIGURE 1.4 Effect of coupling length with function of wavelength.

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1. Photonic crystal fibers for various sensing applications

provides better sensing performance with applied pressure. The resultant pressure sensor is extracted from Eq. (1.6) and follows the stress-optics coefficient principle:
 nx ¼ n0 þ C1 sx þ C2 sy þ sz (1.6) ny ¼ n0 þ C1 sy þ C2 ðsx þ sz Þ The Eq. (1.6) shows that the variation of stress ðsÞ in two different modal axis of fiber which leads to change in refractive index for two orthonormal polarized modes. Hence, it is clear that the variation in stress is directly correlated to birefringence and tends to vary with the function of pressure. The first two components of the index are considered because it has two orthonormal polarizations and includes a two-dimensional structure. The deformed PCF structure caused by applied stress is depicted in Fig. 1.5. It also shows that the effect of phase modal birefringence depends on the stress (Eq. 1.7): dB BLoaded  Bunloaded ¼ dP P

(1.7)

The stress-optic coefficients defined as C1 ¼ 0:69  1012 Pa1 and C2 ¼ 4:2  1012 Pa1 are the stress-optic coefficients for silica; sx ; sy ; sz are the principal components of the induced stress [41]. The impact of transmission spectrum with the function of pressure is calculated from Eq. (1.8). It depends upon sensor length L: PðlÞ ¼

sin2 ðDneo pLÞ l

(1.8)

The difference in transmission spectrum and its spectral shift is plotted in Fig. 1.6. The incremental pressure gives the red shift of the spectrum over the wavelength region.

FIGURE 1.5

Deformed highly birefringent photonic crystal fiber after stress applications.

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1. Introduction to photonic crystal fiber

FIGURE 1.6 Output spectrum shift with respect to external pressure application.

TABLE 1.1

Variation of index difference for different pressure quantities (MPa). Dneo

Pressure (MPa)

l [ 1.4 (mm)

l [ 1.45 (mm)

l [ 1.5 (mm)

l [ 1.55 (mm)

l [ 1.6 (mm)

100

0.010383

0.010389

0.010399

0.010421

0.010446

300

0.01117

0.011168

0.011183

0.011202

0.01123

500

0.01199

0.011983

0.011999

0.012017

0.012043

700

0.012843

0.012835

0.01285

0.012865

0.012889

900

0.01373

0.013721

0.013735

0.013748

0.013769

The corresponding refractive index difference is also calculated and given in Table 1.1 for a particular wavelength from 1.4 to 1.6 mm. The effect of birefringence is enhanced from the minimum to maximum value when applied pressure is varying. For example, the refractive index difference of 900 MPa is 0.1373 at 1.4 mm and it increases when the wavelength is increased to 1.6 mm. It is the highest index difference compared with other pressure values. In addition, the spectral shift is gives the linear variation in applying external pressure. The maximum pressure can be up to 900 MPa and it does not break the fiber, whereas it offers higher birefringence up to 102. The extracted point of wavelength shift is plotted in Fig. 1.7. The corresponding sensitivity is calculated as in Eq. (1.9): S¼

DlP Dn

(1.9)

where DlP represents the peak wavelength and Dn represents the change of refractive index with function of pressure.

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1. Photonic crystal fibers for various sensing applications

FIGURE 1.7 Variations in spectral shift with function of pressure.

Fig. 1.7 gives the overall pressure sensor performance through its wavelength spectral shift. Because it has linear curve characteristics with the function of pressure, the uniform sensitivity from Eq. (1.9) is obtained as 31.2 pm/MPa and it has the maximum of sensitivity than the previously reported pressure sensor. At this stage, it would be worth comparing the results of Hu et al. [41]. They presented side hole dual core PCFs, which promise to yield a pressure sensitivity of 32 pm/MPa using a 10 cm fiber length. This sensitivity is valid up to 500 MPa pressure, whereas we report a pressure sensitivity of 31.2 pm/MPa using just a 1 cm fiber length. This sensitivity is well stable up to 900 MPa. The elliptical hole is introduced in the core region to attain asymmetry and it features an elliptical core path. The designed structure holds higher birefringence with the function of the wavelength. We can observe from these studies that increasing the applied hydrostatic pressure leads to high sensitivity owing to increases in the fundamental mode area. We attained a sensitivity of about 31.2 pm/MPa for a 1 cm length of our proposed PCF sensor, which to our knowledge is much higher than other sensors reported so far with the high birefringence value of 1:2  102 : From the coupling length versus wavelength, the transmission versus Dn and birefringence versus wavelength graphs were been plotted.

1.6 Phase change materialeassisted photonic crystal fiberebased biosensor Photonic crystals are potential candidates in the field of photonic biosensors, especially in the detection of DNA/RNA, viruses, proteins, cancer cells, and glucose solutions. Moreover, surface plasmon resonance (SPR)-based biosensors have opened the window for optical devices with enormous potential for health care applications by offering advanced sensors, imaging devices, and photonic therapies [42,43]. Many works on PCF-aided SPR-based sensors with enhanced sensitivity have been reported [44,45]. Through engineering, nanostructures including plasmonic metamaterials, which are supports for plasmonic resonance, have

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been projected for enhancing the detection limit of plasmonic material-based biosensors [46,47]. The D-shaped PCF structure has received greater attention for SPR sensing applications because the metal layer can be directly deposited on the cleaved flat surface [48e50]. To realize strong and tunable lightematter interaction, graphene has been successfully integrated with PCF [51]. By achieving a switching structural state from amorphous to crystalline, the refractive index of the phase change material (PCM) thin film can be tuned; as a result, the optical properties of the device can be changed. Different PCM thin films have widely been used in several nanophotonic and plasmonic systems to tune their optical functionalities [52,53]. Furthermore, PCMs such as Ge2Sb2Te5 (GST) contain some remarkable properties, especially because they can be reversibly switched at the subnanosecond scale billions of times. PCM-based optical devices have shown better performance over liquid crystals and mechanically tuned photonic devices [54]. Here, we use GST as the PCM owing to its low-loss and large refractive index in contrast to the NIR wavelength regime. We demonstrate the wide-range tunability of the designed structure in refractive index sensing with extreme sensitivity by using the nonvolatile phase change properties of GST. The proposed reconfigurable refractive index sensor can be used to tune the spectral position of the modes in the infrared frequencies; hence, vibrational fingerprints of various biomolecules can be determined, which is needed for infrared spectroscopy. Fig. 1.8A and B shows cross-sectional and three-dimensional views of the proposed D-shaped PCF sensor, respectively. In the D-shaped PCF, three layers of air holes are arranged as a triangular lattice. Spacing between two air holes in each layer is 2 mm. FIGURE 1.8 (A) Cross-sectional view of D-

shaped photonic crystal fiber; (B) Cross sectional view of D-shaped photonic crystal fiber. GST, Ge2Sb2Te5.

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1. Photonic crystal fibers for various sensing applications

The optimized value of the diameter for two big air holes is 2.4 mm and the rest have a diameter of 1.2 mm. An important layer in the proposed PCF sensor is the hybrid sensing layer of Au/GST, which offers tunable and enhanced refractive index sensing through the evanescent wave sensing mechanism. The optimized thickness of the GST and Au layer is 14 and 12 nm, respectively. The coupling condition between the decaying evanescent fields surface plasmon polaritons (SPP) at the hybrid layer of Au/GST with the core mode of the fiber is essential for sensing. Strong coupling between the silica core mode and SPP mode is attained owing to high birefringence in the fiber by making big air holes close to the core region. By means of the finite element method, we study the performance of the proposed PCF sensor. Fused silica is used as the background material of the sensor; we obtained the wavelength-dependent refractive index of silica from the Sellmier equation [55]: n2  1 ¼

3 X Ai l2 2 2 i ¼ 1 l  li

(1.10)

In Eq. (1.10), n is the refractive index of fused silica and li and Ai are the fitting parameters with the values of l1 ¼ 0.0684043, l2 ¼ 0.1162414, l3 ¼ 9.8961611, and A1 ¼ 0.6961663, A2 ¼ 0.4079426, and A3 ¼ 0.8974794. Using the Drude model, the wavelength-dependent complex permittivities of gold can be calculated as [56]: ε ¼ 1

u2p u2 þ iuGp

(1.11)

where up and Gp are the plasma frequency and damping rate, respectively, which are up ¼ 9:062 eV and Gp ¼ 0:070 eV. The loss values (a (y)) in dB cm1 are calculated by using the expression: aðyÞ ¼ 8:686 

2p
 Im neff  104 l

(1.12)

As shown in Fig. 1.9A, the SPP mode and the silica core mode are coupled at a wavelength of 1.26 mm for aGST. In particular, the effective indexes of both modes are close to each other and loss values are matched at the coupling wavelength. This perfect coupling is achieved owing to the low absorption of aGST at 1.26 mm. In the case of cGST, coupling happened at a wavelength of 1.38 mm, as depicted in Fig. 1.9B. The observed increase in coupling wavelength is due to the increase in the refractive index of GST from amorphous to crystalline phase transition. aGST and cGST respectively denote the amorphous phase GST and crystalline GST. The refractive index span covers the refractive index of unknown analytes such as DNA/RNA, viruses, proteins, cancer cells, and glucose solutions [57,58]. As depicted in the figures, when switching the phase of the GST layer from amorphous to crystalline, we observe large tunability in the NIR wavelengths. The wavelength tunability increases with an increase in the refractive index value of the analyte, because the obtained wavelength shift for 1.35 and 1.4 is 20 nm (Fig. 1.10A) and 500 nm

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FIGURE 1.9

Effective index and loss spectrum of fundamental silica core mode (guided mode) and SPP mode of Au/GST layer when GST is in (A) amorphous phase (aGST) and (B) crystalline phase (cGST).

(Fig. 1.10F), respectively. Furthermore, resonance (peak) wavelengths are red shifted with an increase in the refractive index of the analyte. As a result, the wavelength shift increases, because the refractive index contrast between the amorphous and crystalline phase increases with an increasing wavelength up to 2 mm. In particular, extraordinary tunability with a two-times increase in sensitivity is obtained by switching the phase of the GST from amorphous to crystalline. Because the refractive index of cGST is compared with the aGST in the NIR wavelengths, higher field confinement is possible for cGST [59]. As a result, maximum sensitivity is obtained when the GST thin film is in crystalline phase.

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1. Photonic crystal fibers for various sensing applications

FIGURE 1.10 Transmission loss spectrum for both phases of GST when the refractive index of analyte changes from (A) 1.35 to (F) 1.4 at intervals of 0.01.

We then calculated the minimum detectable refractive index limit or resolution of the sensor, which can be calculated [48]:   Dlmin Resolution ¼ Dna  (1.13) Dlpeak In the Eq. (1.13), lmin denotes the minimum spectral resolution and is fixed as 0.1 nm. The calculated resolution value of the proposed sensor is 1.251  105 refractive index unit (RIU) for aGST and 5.555  106 RIU for cGST and cGST. We attained higher resolution for cGST, which implies that the sensor detects smaller refractive index changes when GST is in crystalline phase. By calculating the optical power loss with respect to the refractive index analyte at a fixed wavelength, we studied the tunable amplitude sensitivity of the sensor using the expression [60]: 
Da l; nanalyte =Dnanalyte
 Sa ¼ (1.14) a l; nanalyte 
where a l; nanalyte is the confinement loss of fundamental mode at a particular wavelength and analyte refractive index.

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References

FIGURE 1.11 Transmission loss spectrum of photonic crystal fiber sensor without GST layer sensor for different refractive indices of the analyte.

The proposed sensor provides an extreme average refractive index sensitivity of 17,600 nm/ RIU when GST is in crystalline phase, which is a higher value compared with existing PCF sensors. In particular, the sensitivity can be tuned between 8000 and 17,600 nm/RIU, which is the most important feature of the proposed PCF sensor. To ensure the impact of the GST layer in the designed sensor, we investigate the sensing performance of the PCF sensor in the absence of a GST layer. We calculated the refractive index sensitivity (2000 nm/RIU) and resolution (2.501  105 RIU) of the PCF sensor without a GST layer. The result confirmed an eightfold increase in sensitivity, which confirms that cGST with a much higher resolution is obtained in the presence of a GST layer of a D-shaped PCF SPR sensor. The transmission loss spectrum of this sensor with different refractive indices of analyte is shown in Fig. 1.11. Compared with the PCF sensor with GST layer, we conclude that the resonance peak wavelengths resulted at lower wavelengths owing to the absence of the GST layer. By achieving the switching behavior of the GST layer from amorphous to crystalline, the average refractive index sensitivity is attained from 8000 to 17,600 nm/RIU for an analyte refractive index range of 1.35e1.4. The designed PCF sensor is a potential candidate for biosensing applications, especially cancer cell detection.

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Shah Alam, Design of a polarization-maintaining equiangular spiral photonic crystal fiber for residual dispersion compensation over wavelength bands, IEEE Photon. Technol. Lett. 24 (11) (2012) 930e932. [40] M. Sharma, N. Borgohain, S. Konar, Supercontinuum generation in photonic crystal fibers possessing high birefringence and large optical nonlinearity, Phys. Exp. 4 (2015) 1e9. [41] G. Hu, D. Chen, Side-hole dual-core photonic crystal fiber for hydrostatic pressure sensing, J. Lightwave Technol. 30 (14) (2012) 2382e2387. [42] K.V. Sreekanth, S. Sreejith, Y. Alapan, S. Metin, C.T. Lim, R. Singh, Microfluidics integrated lithography free nanophotonic biosensor for the detection of small molecules, Adv. Opt. Mater. 7 (7) (2019) 1801313. [43] I. Hyungsoon, H. Shao, Y.I. Park, V.M. Peterson, C.M. Castro, R. Weissleder, H. Lee, Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor, Nat. Biotechnol. 32 (5) (2014) 490. [44] S.A. Mitu, K. Ahmed, F.A. 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Zhang, D-shaped photonic crystal fiber refractive index sensor based on surface plasmon resonance, Appl. Opt. 56 (24) (2017) 6988e6992. [49] S. Shivam, Y.K. Prajapati, Highly sensitive refractive index sensor based on D-shaped PCF with gold-graphene layers on the polished surface, Appl. Phys. A 125 (6) (2019) 437. [50] T. Zhixin, X. Li, Y. Chen, P. Fan, Improving the sensitivity of fiber surface plasmon resonance sensor by filling liquid in a hollow core photonic crystal fiber, Plasmonics 9 (2014) 167e173. [51] K. Chen, X. Zhou, X. Cheng, R. Qiao, Y. Cheng, C. Liu, Y. Xie, W. Yu, F. Yao, Z. Sun, F. Wang, Graphene photonic crystal fibre with strong and tunable lightematter interaction, Nat. Photonics 13 (2019) 754e759. [52] K.V. Sreekanth, S. Han, R. Singh, Ge2Sb2Te5 based tunable perfect absorber cavity with phase singularity at visible frequencies, Adv. Mater. 30 (2018) 1706696. [53] P. Prakash, A. Kumar, S. Prakash, H. Jani, T. Venkatesan, R. Singh, Chalcogenide phase change material for active terahertz photonics, Adv. Mater. 31 (2019) 1808157. [54] S. Abdollahramezani, O. Hemmatyar, H. Taghinejad, A. Krasnok, Y. Kiarashinejad, M. Zandehshahvar, A. Alu, A. Adibi, Tunable nanophotonics enabled by chalcogenide phase change materials, Nanophotonics 9 (5) (2020) 1189e1241. [55] I.H. Malitson, Interspecimen comparison of the refractive index of fused silica, JOSA 55 (10) (1965) 1205e1209. [56] R. Elghanian, J. Storhof, R.C. Mucic, R.L. Letsinger, C.A. Mirkin, Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles, Science 277 (1997) 1078e1081. [57] D. Lorena, N. Darwish, M. Mir, E. Martínez, M. Moreno, J. Samitier, Effect of the refractive index of buffer solutions in evanescent optical biosensors, Sens. Lett. 7 (5) (2009) 851e855. [58] N. Ayyanar, G.T. Raja, M. Sharma, D.S. 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C H A P T E R

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An overview of nanomaterialenhanced miniaturized/microfluidic devices for electrochemical sensing Khairunnisa Amreen and Sanket Goel MEMS, Microfluidics and Nanoelectronics Lab, Department of Electrical and Electronics Engineering, Birla Institute of Technology and Science, Hyderabad, Telangana, India

1. Introduction Nanotechnology is deployed to design nanomaterials (NMs) strategically with desired properties [1]. Their speedy advancement has revealed an extensive array of prospects for applications in electrochemical sensing [2]. These NMs possess properties different from other micro- and macroparticles, including a high surface area, excellent electron conductivity, electrocatalytic activity, mechanical, magnetic and electrical properties, high tensile strength, and stability [3,4]. Using nanoarchitectonics [5,6], complex nanostructures with desired functions are engineered. Interactions of NMs with physiologic biomolecules have been used for biosensing [7]. NMs such as carbon [8], metal and metal oxide [9,10], polymeric [11], quantum dots (QDs) [12,13], nanorods, and tubes have been used for scheming sensors. By encapsulation or linkages, these materials can be conveniently modified [14]. There is a robust association between NMs and miniaturized/microfluidic electroanalytical biosensing systems. Nanoparticles are advantageous for upgrading electrochemical sensing. Several proteins, DNA, RNA, cells, biomarkers, biochemicals, pollutants, heavy metals, and so on have been detected via the electrocatalytic behavior of NMs [15e17]. NMs can be used to load signals [18]. NMs with a quantum tunneling effect [19] or quantum size effect have superior properties over conventional macro- or microparticles [20]. NMs are classified based on their dimensions into three categories: (1) 0-dimensional (0D), (2) 1D, and (3) 2D [21]. Based on their morphologic nature, NMs are selected for various applications, especially in microdevices. Microfluidic/miniaturized devices, otherwise known as lab-on-chip (LOC) devices, have witnessed substantial progress since the early 1990s [22,23]. These devices assimilate various laboratory techniques over a small chip of dimensions varying from millimeters to

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centimeters [24]. These advances have opened a gateway to designing analytical detection systems [25]. The devices offer fewer sample requirements, reduced reagent use, portability, and cost-effectiveness [26]. Microfluidic platforms for the detection of various bioanalytes have been designed [27e29]. Since their applications have grown extensively, various possible materials for fabrication are being explored. Earlier, only silicon and glass were preferred, but elastomers such as polydimethylsiloxane (PDMS), poly(methyl methacrylate), polycarbonate, and cyclic olefins are also being explored [30]. NMs have proven to enhance the activity of these microdevices. Electroanalytical sensing and microfluidics share a synergetic relation. On the one hand, microfluidics gives LOC and point of care testing systems (POCTS) [31]. On the other hand, electrochemical techniques can easily be miniaturized. Similarly, the symbiosis of electrochemical sensors and NMs is expected to result in augmented applications [17,32]. The integration of electrochemical techniques in microdevices has gained a lot of attention. Furthermore, surface modification of integrated electrodes with NMs has increased sensing ability [32e35]. Henceforth, the combination of microdevices, NMs, and electroanalytical sensing can be termed a marriage of expediency. This chapter mainly focuses on advances in NM-integrated microdevices for multiple electrochemical sensing applications. Brief information about the synthesis and design of microdevices and electrodes, surface modifications, and so forth from various research groups globally will be discussed. Examples and future perspectives are also examined.

2. Synthesis of nanomaterials Since the 1970s, there has been tremendous growth in various strategies of fabricating nanoparticles with desired features and morphology. There are basically three major methods of fabricating nanoparticles: (1) chemical: hydrothermal, sol-gel, emulsion, electrochemical deposition, or complex deposition is carried out [36,37]; (2) mechanical or physical: grinding, laser sputtering, ion beam sputtering, evaporation, or condensation is adapted [38]; and (3) comprehensive: plasma-enhanced, ultrasonication-based and gas phase synthesis are followed [39]. In any way of fabrication, the principle of nanoparticle formation depends on two major routes: (1) the bottom-up-approach, in which NMs develop by forming clusters through a molecular and atom-to-atom arrangement; and (2) the top-down-approach, which breaks down a bulk material into the desired morphologic shape and size [40,41].

2.1 Advances in strategically engineered nanomaterials There has been tremendous growth in strategically engineered NMs with desired properties, such as for cancer theranostics [42], graphene-based NMs [43], 2D NMs for gene delivery [44], to control friction [45], for medical biomarkers [46], biogenics [47], ZnS QDs [48], biomedical use [49], Li/NaeS [50], energy [51], black phosphorous [52], drug delivery [53], purification of water [54], label-free sensing [55], magnetic hybrids [56], water decontamination [57], oil separation [58], environment remediation [59], cellulose-based NMs [60], agriculture [61], ZnO NMs for flexible devices [62], 2D MoS2 bioimaging [63], energy storage [64], plasmonics [65],

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stretchable NMs [66], enzymatics [67], 0D NMs for photocatalysis [68], polyaromatic hydrocarbons [69], peroxides [70], antioxidatives [71], magnetohydrodynamic NMs [72], antimicrobial activity [73], wound healing [74], nucleic acids [75], anticorrosion [76], electrochemiluminescence [77], superlubricity [78], batteries [79], water remediation [80], chemotherapy [81], colorimetric [82], DNA sensing [83], antivirals [84], photodynamics [85], imaging [86], food supplements [87], biogas [88], biorecognition [89], plant protection [90], enantioseparation [91], cancer therapy [92], bone engineering [93], distillation [94], diagnostics [95], environmental uses [96], tissue engineering [97], and augment photosynthesis [98].

3. Nanomaterial-based electrochemical sensing In several fields, an NM-based electrochemical sensing approach has been deployed. Some important applications are discussed next.

3.1 Nanomaterial-dependent immunosensors The antigen-antibody based immunosensing has grown substantially [99]. As can be seen in Fig. 2.1, a typical immunosensor preparation using the sandwich model is shown. Surface modification of the desired conducting electrode or material with NMs is done. This increases the surface area; hence, an antigen-antibody complex is easily formed [100]. Some of similar examples are for pancreatic cancer detection [101], pesticides and herbicides [102], ovarian cancer [103], microbial toxins [104], tumor markers [105], and foodborne pathogens [106].

3.2 Nanomaterial-dependent electrochemical sensors: biomedical applications NMs are further functionalized with different redox mediators and electrochemically active biomolecules. The most frequently used NMs in this regard are carbon-based [107]. Chen et al. summarized some of these notable electrochemical sensors reported in the literature [108]. FIGURE 2.1 Schematic diagram of an immunosensor. Reprint with copyright from Zhang et al.

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3.3 Nanomaterial-dependent electrochemical sensors: heavy metal detection Heavy metals such as mercury, cadmium, arsenic, and lead can cause serious illness [109]. Traditionally, the analysis of these metals is done through spectroscopic techniques, which are lab-based procedures [110]. For ease of operation, electrochemical techniques are usually preferred. The modification of electrodes with desired NMs improves the sensing ability. In 2018, Waheed et al. summarized some of these significant research works [111].

4. Microfluidic/miniaturized device fabrication Approaches to fabricating microfluidic devices are being explored (Fig. 2.2).

4.1 Soft lithography This method involves replica molding [112]. Materials such as PDMS are used. A master mold is made through micromachining. The liquid polymer, which is mixed with a curing agent, is poured over the master stamp, which has designed patterns. Upon heating, it solidifies the material [113].

4.2 Photolithography This method uses optical beams to sketch patterns on the base material [114].

4.3 Three-dimensional printing This is a technique of layer-by-layer material deposition. Various conductive filaments such as acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), polyethylene terephthalate (PET), wood fiber (cellulose plus PLA), and polyvinyl alcohol are used [112].

FIGURE 2.2 Schematic for various types of microdevice fabrication techniques. 3D, three-dimensional.

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4.4 Laminates This method is composed of piling (stacking) and bonding individually cut layers to form a secure device [112].

4.5 Molding This method involves developing a master mold using a photolithography method. Liquefied polymer is poured over this mold followed by curing and then solidifying [112].

5. Nanomaterial-enhanced microfluidic/miniaturized devices for electrochemical sensing NMs are most commonly used to improve detection limits in microdevices. Chen et al. reported carbon nanotubes (CNTs) and graphene composites for microfluidic systems [115]. Okuno et al. fabricated a label-free immunosensor. Platinum microelectrodes array combined with CNTs were used for the analysis [116]. Fig. 2.3A shows an image of their device [116]. Vlandas et al. designed an enzyme-less CNT sensor for the analytical detection of sugars. Fig. 2.3B shows the device’s schematic [117]. Wijaya et al. prepared a microfluidic system for the femtomolar-level detection of 2,4-dichlorophenoxyacetic acid with a CNT liquid gated transistor [118]. Chua et al. demonstrated a graphene-based device for amperometric detection of nitroaromatic and catechol. Fig. 2.3C is a schematic diagram of the device [119]. He et al. revealed a reduced graphene oxide-based thin film transistor over a PET substrate for fibronectin detection [120]. Zou et al. developed a nanoparticle interdigitated/gold electrode array. Fig. 2.4A shows a schematic of the device form Zou et al. [121].

FIGURE 2.3A

Experimental setup and microarray schematic representation. CE, counter electrode; SWNTs, Single walled carbon nanotubes; T-PSA, total prostrat specific antigen. Reprinted with copyright from Okuno et al.

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FIGURE 2.3B

Schematic representation of the microdevice for sugar sensing. Reprinted with copyright from Vlandas

et al.

FIGURE 2.3C Schematic representation of the microdevice. PDMS, polydimethylsiloxane. Reprinted with copyright from Chua et al.

Likewise, Lee et al. established a conductometric enzyme array for biosensing using indium oxide nanoparticles. Fig. 2.4B shows the device [122]. Wang et al. reported a polypyrrole graphene-based microelectrode array for dopamine detection from neural cells [123]. Karuwan et al. designed a graphene electrodes integrated microfluidic device for glutathione detection [124]. Medina-Sanchez et al. made a PDMS-based chip device to detect atrazine, a pesticide [125]. Benuzzi et al. fabricated a glass/PDMS-bonded microchip device with Cu nanoparticles to detect cystic fibrosis biomarkers [126]. Brinc et al. invented a microchip with a nonlithographic approach in which a multiwalled CNT-zinc oxide nanofiber-modified gold electrode

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FIGURE 2.4A Interdigitated nanoelectrode array microfluidic device. Reprinted with copyright from Zuo et al.

FIGURE 2.4B Schematic representation of their microdevice. INP, indium oxide (In2O3) nanopowders; PDDA, polydiallyldimethylammonium chloride; PSS, sodium polystyrene sulfonate. Reprinted with copyright from Lee et al.

was used to detect histidine-rich protein [127]. Malhotra et al. designed a microfluidic array enhanced by nanostructures to detect four oral cancer biomarkers [128]. Similarly, Chikkaveeraiah et al. prepared a multiplexed electrochemical immune assay of protein cancer biomarkers in serum using a gold nanoparticle working electrode [129].

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FIGURE 2.5A Experimental setup and device. GMC, graphitized mesoporous carbon; ITO, indium titanium oxide; RE, reference electrode; WE, working electrode. Reprinted with copyright from Sun et al.

Microfluidic paper-based analytical devices (mPADs) are also reported. Most are disposable and are used as POCTS [130]. Whitesides et al. reported cutting-edge research about these [131]. mPADs have certain limitations in terms of their sensitivity, slower reaction rate, and poor stability. To overcome these, they are modified [132]. For example, Li et al. fabricated ZnO nanoparticle mPADs for glucose sensing [133]. Sun et al. prepared a paper device for the in situ determination of salicylic acid in tomato leaves. Fig. 2.5A is the reprint from Sun et al. [134]. Ge et al. offered a mPAD with gold nanoparticle-decorated cellulose fibers to detect D-glutamic acid [135]. Zhang et al. developed a 3D microfluidic origami device as an immunosensor [136]. Yan et al. designed a carbon screen printed immunosensor to detect prostate-specific antigen [137]. Wu et al. fabricated a device to detect cancer biomarkers [138]. That research group demonstrated nanobioprobes and graphene films devices [139]. Li et al. developed an origami device immunosensor with silver/chitosan composite [140]. Lei et al. established a paper device for a label-free immune assay of avidin [141]. Lu et al. developed 3D paper microdevice with graphene/gold nanoparticles for DNA detection [142]. Szucs et al. reported a mPAD with aptamer and silver nanoparticle conjugates to detect immunoglobulin E (IgE) [143]. Su et al. designed a mPAD to detect cancer cells [144]. That research group used Pt nanospheres over a working electrode, followed by binding aptamers to capture cancer cells [145]. Shi et al. developed a platform with a CNT/graphene/MnO2 aerogel for H2O2 detection [146]. Hu et al. established an oxygen sensor over cellulose using ionic liquids/gold nanoparticles [147]. Ge et al. fabricated A nitrocellulose membrane test strip with AN Fe3O4@TiO2 composite for biomarkers [148]. QDs are also used in microfluidic devices. Liu et al. used CdS@ZnS QDs to detect IgE [149]. Nantaphol et al. developed a paperbased device boron-doped diamond paste working electrode modified with reduced graphene oxide to detect serotonin and norepinephrine [150].

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Significant reports have been published by our group as well. For instance, Mohan et al. developed an ink-jet printed miniaturized platform for biosensing using graphitized mesoporous carbon (Fig. 2.5B) [151]. A miniaturized graphite paper/CuO nanostructure-based platform for hydrazine detection was realized (Fig. 2.5C) [152]. Salve et al. developed a three-electrode miniaturized platform using Bucky paper as three electrodes for xanthine and uric acid sensing (Fig. 2.6A) [153]. Kothuru et al. fabricated a microfluidic device using a polyimide sheet as a substrate with laser ablation to form laser-induced graphene for uric acid testing (Fig. 2.6B) [154]. Salve et al. also fabricated a platform with three electrodes using an multiwalled carbon nanotube (MWCNT)@polysterene-chitosan nanocomposite. The device was tested for enzyme-less glucose sensing (Fig. 2.7A) [155]. A microfluidic device for supercapacitor and electrochemical sensing application with silver nanoparticles was also reported by Salve et al. (Fig. 2.7B) [156]. Amreen et al. developed a 3D printed platform with an ABS filament for hydrazine (Fig. 2.7C) [157].

FIGURE 2.5B

Schematic of ink-jet printed electrochemical platform formation. Reprinted with copyright permission

from Mohan et al.

FIGURE 2.5C

Schematic of three-electrode paper-based miniaturized platform for hydrazine sensing.

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FIGURE 2.6A

FIGURE 2.6B

Image of platform.

Schematic of device fabrication. Reprinted with copyright permission from Kothuru et al.

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FIGURE 2.7A Reprinted with copyright permission from Slave et al.

FIGURE 2.7B

LED powered by three-dimensional printed cells connected in series. Reprinted with copyright permission from Salve et al.

FIGURE 2.7C

Image of microfluidic device and setup. Reprinted with copyright permission from Amreen et al.

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6. Conclusions and outlook The association of microfluidics, nanotechnology, and electrochemical sensing has significantly advanced the development of microdevices with point of care analysis. This chapter gives an overview about the use of various structurally engineered NMs for electrochemical sensing in microfluidic and miniaturized platforms. A few examples about how NMs have enhanced the analytic performance of microfluidic electrochemical devices are discussed here. Not only carbon-based, but also metal-based, polymer-based, and other types of NMs are employed in these devices. Drop casting, fully automated ink jet printing, screen printing, and electrodeposition method are used to modify electrodes with NMs. Paperbased devices have been observed to grow more rapidly than others owing to their low cost, availability, portability, and biocompatibility. However, these mPADS have limitations in terms of specificity and reproducibility. NMs to fabricate mPADS have become the most attractive research mode. NMs significantly enhance the performance of these paper devices, and it is anticipated that they will attract more attention in future for biosensor, diagnostic, and genosensing applications. However, these are still in the development phase and have several challenges to be overcome in terms of LOC devices. As the paper substrate allows the incorporation of NMs within its matrix, future possible devices cannot help in detection but also in separation, isolation, purification and synthesis. In this context, NMs will have an extraordinary impact on enhancing the sensitivity of next-generation paper devices. We expect that in the future, genetics, electronics, and immunology can also be incorporated into these devices and thus will influence health management positively. Broader implementation of these devices needs higher access to the health sector. Overall, NMs incorporated in microfluidic devices are a well-established and promising research area in which in each passing day new materials can be structurally designed and incorporated based on the applications.

Acknowledgments Khairunnisa Amreen would like to acknowledge SERB NPDF Scheme PDF/2018/003658 for financial assistance.

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Approaches for synthesis of nanocrytals: an overview Gita Rani and Anu Bala Department of Chemistry, Chaudhary Devi Lal University, Sirsa, Haryana, India

1. Introduction Nanocrystals can be prepared by different methods. In general, comminution (top-down) and precipitation (bottom-up) are two technical approaches used for synthesis [1]. A bottomup approach such as solvent precipitation starts from the atom and grows it into nanoscale crystals, whereas a top-up approach such as milling fragments perceptible particles to nanocrystals [2]. A pretreatment step followed by high-energy size reduction are employed in the combination approach [3]. The formulation of nanocrystals is obtained in the form of a nanosuspension. However, the problem of aggregation and Ostwald ripening result in a liquid state product with short-term stability. The solidification of particulates solves these problems is more convenient for dispensing and shipping. The dried form of particles can be easily obtained by eliminating the solvent from the resulting suspension [4]. Freeze-drying and spray-drying are the best technologies for solidifying nanosuspensions and are categorized as bottom-up approaches. Spray-drying is more popular than freeze-drying because of its cost- and time-effectiveness; hence, it is suitable for industrial purposes [5]. The topdown approach is more suitable for the commercial production of nanocrystals but it has limitations for particle size reduction and it takes more time to reduce particle sizes >100 nm. Unlike the top-down synthesis approach, particles produced by the bottom-up process have a narrow size distribution, but the problems of stability and particle growth are major concerns. A combination of both top-down and bottom-up approaches is also available for the industrial feasibility of nanocrystal production. Further classifications of these important techniques are shown in Fig. 3.1.

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FIGURE 3.1

Synthesis approaches to nanocrystals.

2. Top-down approaches Top-down techniques are high-energy processes that involve the fragmentation of larger solid particles into nanoscale crystals step-by-step through mechanical processes. The mechanical energy thus imparts stress to particles that are strained and then deformed into nanoscale particles. Top-down approaches have the drawbacks of high energy consumption and wear and tear on equipment [6,7]. Wet bead milling and high-pressure homogenization (HPH) are important top-down approaches as described subsequently.

2.1 Wet bead milling Wet bead milling (WBM) is a first-generation synthesis approach frequently used to fabricate nanocrystals on a large scale. It alters the size as well as the surface roughness and shape of particles [8]. An active drug agent in the presence of a surface stabilizer is

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comminuted into a nanosuspension by milling media. The suspension is poured in the grinding container along with beads, and the beads are rotated at a very high speed [9]. Stress intensity, which is the function of the kinetic energy of the grinding beads, determines the particle size [10]. Because the milling process usually involved milling beads, it is often called wet milling ball or pearl milling [11]. The milling beads are available in different sizes and are made of glass or stainless steel. Frequently, the beads are made of ceramic (such as yttrium-stabilized zirconium dioxide) or highly cross-linked polystyrene resin because there is less risk of contaminating active drug particles [12]. It is a waterbased approach and involves no organic solvents with low batch-t- batch variations [13]. Wet milling is a universal and versatile technique that processes a variety of drugs with poor water solubility into nanosuspensions and enhances their dissolution rate [14]. An increase in the milling speed and milling time, and the size reduction of beads often yields small particles [15]. Nanocrystals of progesterone, cyclosporine A, resveratrol, hesperetin, ascorbyl palmitate, apigenin, and hesperidin are produced by WBM [16,17]. Also, WBM is used to fabricate semiconductor nanocrystals, also known as quantum dots, such as colloidal nanocrystals of lead halide perovskites [18].

2.2 High-pressure homogenization HPH is another simple bottom-up technique that employs high pressure to pulverize particles to the nanoscale. Applied pressure is increased step-by-step to avoid clogging the narrow homogenization gap. It includes piston-gap homogenization and jet-stream homogenization techniques [7]. 2.2.1 Piston-gap homogenization A piston-gap homogenizer consists of two chambers, as shown in Fig. 3.2. Macrosuspensions are composed of a drug, stabilizer, and water passed through a thin piston (a few micrometers) with high velocity, shear forces, cavitation forces, and particle collisions, resulting in nanosized crystals [19]. The desired particle size can be achieved by altering parameters such as the applied pressure, temperature, and homogenization cycles. HPH technique was applied successfully to produce nanocrystals like Quercetin nanocrystals. Quercetin nanocrystals prepared by this technique had a high dissolution rate than original Quercetin [20]. Also, nanocrystals of the nonsteroidal antiinflammatory drug piroxicam were prepared with a faster dissolution rate by HPH [21]. 2.2.2 Jet-stream homogenization (microfluidization) Microfluidization is an insoluble drug delivery microparticle technology developed by Skyepharma [22]. The technology involves the jet-stream principle in which two jet streams from two types of chambers (Z-type and Y-type) are forced to circulate under high pressure through a microfluidizer nozzle [23]. Dispersion media containing drugs, stabilizers, and water experience collisions, cavitation forces, and shear stress in these chambers, leading to the disintegration of macroparticles through multiple homogenization cycles [24].

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FIGURE 3.2 Rough representation of high-pressure homogenizer.

3. Bottom-up approaches Bottom-up approaches are commonly called precipitation techniques. The drug is dissolved in an organic solvent and then precipitated out by using an antisolvent or drastic temperature change or by involving supercritical fluids (SCFs) [25]. Some frequently used bottom-down approaches are discussed next.

3.1 Precipitation Simple precipitation methods had difficulties in forming nanocrystals. For the better production of nanocrystals, some advanced techniques such as antisolvent precipitation and precipitation in SCFs were introduced [26]. 3.1.1 Antisolvent precipitation This bottom-up technique is simple and cost-effective and requires no specialized pieces of equipment or high energy input [27]. Usually, an organic solvent is used to dissolve the poorly water-soluble drug and is added to a miscible nonsolvent (generally water) [28]. Supersaturation takes place, resulting in immediate nucleation and precipitation. Particle growth need to be controlled for stabilized nanosuspension. For this purpose, stabilizers such as polyvinyl alcohol, gelatin, poloxamers, and sugars have been added to the drug solution [29]. Significant parameters such as the amount of the main drug, the stirring rate, the volume ratio of antisolvent to organic solvent, the stabilizer type, the ratio of the stabilizer to the drug, and the temperature should be optimized for the better yield of nanocrystals

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[30,31]. With an increase in the stirring rate, mixing on the molecular level between the phases is maximized, which enhances the rate of diffusion of the drug particles and results in higher supersaturation and nucleation. Higher supersaturation is also caused by a high volume ratio of antisolvent to solvent. However, a moderate amount of drug is recommended for better precipitation. A higher amount of drug hinders the two phases because of increased viscosity and nonuniform supersaturation may take place. A lower temperature makes supersaturation easy and favors particle size reduction [32]. 3.1.2 Precipitation in supercritical fluid In particle engineering, SCFs such as carbon dioxide, ethylene, ammonia, and fluoroform are extensively used despite of the toxic nature and flammability of some solvents. However, carbon dioxide is a naturally abundant material. It is nontoxic and nonflammable and has a low critical temperature and pressure (Tc ¼ 31.04 C and Pc ¼ 7.38 MPa), which make it preferable for commercial use [33,34]. The technique is useful for nanoformulations of various drugs, polymers, and nanocomposites [35,36,37]. There are different supercritical techniques, such as the rapid exchange of supercritical solution (RESS), rapid exchange of supercritical solvent in liquid solvent (RESOLV), rapid exchange of supercritical solution solid cosolvent (RESS-SC), supercritical antisolvent (SAS), and other modified techniques [30,38]. In RESS, the compound dissolves in an SCF and expands the dissolved solution in a lowpressure chamber through a narrow nozzle. The difference in the pressure of the chambers changes the density of the fluid, resulting in supersaturation and finally precipitation. The modified process of RESS is RESOLV, in which nozzle expansion is kept under the solvent rather in the air/gas phase [39,40]. In addition, another technique, RESS-SC, is used a solid co-solvent besides SCF to increase the solubility of compounds in CO2. Usually, methanol is used as a solid co-solvent [38]. Some compounds are not dissolved in SCF and cannot be processed by RESS. This limitation of the RESS technique can be overcome by an SAS technique that works on the principle that SCFs have poor affinity with solute but high affinity with organic solvents. The drug is dissolved in an organic solvent and sprayed into SCF, or SCF can be added to the drug solution. The organic solvent diffuses in SCFs and the drug precipitates out owing to poor solubility in the SCFs [41,42].

3.2 Solvent evaporation Besides these precipitation methods, controlled precipitation by the removal of solvent has been widely accepted for nanocrystal production. It can be done by spray-drying or freeze-drying. Both processes involve organic solvents to dissolve the compounds. In the case of spray-drying, solvent selection depends on the boiling point and toxicity of the solvent. Too-low and too-high boiling points are not favorable because of ignition and evaporation issues, respectively. The boiling point of the organic solvent must be lower than the melting point of compounds in the process [43,44]. Atomization of the liquid (containing the compound) is then carried out by an atomizer using a hot air current, resulting in dry particles [45]. However, in freeze-drying, solvent elimination is done by instant freezing of the sample solution by liquid nitrogen [44]. The organic solvent used in the procedure must have a low freezing point and high vapor pressure so that the solvent crystallizes completely during freezing. Unlike the spray-drying technique, working at low temperatures

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in freeze-drying is more suitable for thermolabile compounds such as proteins [46]. The two processes have the advantage of removing organic solvent residue and share the limitations of being costlier in terms of operation and equipment [44].

4. Combination approaches Combined technology employs both top-up and bottom-down technologies to achieve high efficiency for the production of uniform, well-distributed nanocrystals. From a commercial and economical point of view, a combined approach for particle size reduction is highly recommended to overcome the limitations of high energy input and the high risk for contamination in standard technologies. To minimize the number of homogenization cycles or the milling times, the top-down approach is combined with a bottom-down process [47]. Pretreatment step includes the bottom-up technology in which the drug is precipitated, followed by a high-energy mixing step using a top-down approach. For example, glibenclamide drug nanocrystals were obtained by a combined technology of nonaqueous freeze-drying followed by HPH [48]. Five combinative techniques are NANOEDGE (precipitation followed by HPH), cavi-precipitation/H69 (precipitation instantly followed by HPH), H42 (spray-drying followed by HPH), H96 (freeze-drying followed by HPH), and combinative technology (CT) (wet milling followed by HPH) [49]. 1. NANOEDGE NANOEDGE is a combination technique of precipitation followed by HPH. In precipitation, it is difficult to control the growth of particles. This results in unstable and large particles. Employing a high-energy process such as HPH after precipitation provides thermodynamic stability to precipitated particles by inhibiting particle growth. The combination of these methods provides a better solution that eliminates drawbacks associated with both precipitation and HPH and is suitable for industrial applications [29,50,51]. 2. H69 approach H69 technology, also known as cavi-precipitation, is similar to the NANOEDGE approach, except that cavitation takes place immediately after precipitation. In the combination approach, the compound is dissolved in an organic solvent. Then, the solution is added to an antisolvent, resulting in precipitation. Precipitation is carried out in a high-energy cavitation zone or inhibition zone of the homogenizer. Employing cavitation reduces the production time and prevents uncontrolled particle growth. However, organic solvent residue is the major drawback of the H69 technique, as in the case of NANOEDGE [51]. 3. H42 approach This technology employs the combination of spray-drying precipitation and HPH. Compounds such as drugs are dissolved in an organic solvent in the presence of stabilizers such as poloxamers and sugars. The organic solvent must be suitable in terms of the boiling point and vapor pressure to ensure the yielded product is free of solvent residues. The nanosuspension of spray-dried products is processed under the HPH approach. H42 comes with

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4. Combination approaches

the advantage of the elimination of organic solvent residues, which is a limitation of both NANOEDGE and H69. However, the involvement of high temperatures during spraydrying makes the technology unfit for thermolabile materials [8]. 4. H96 approach In H96 technology, freeze-drying is a pretreatment step and HPH is a posttreatment step. The drug is dissolved in an organic solvent, freeze-dried, and redispersed, and instantly goes through homogenization. Freeze-drying is the immediate freezing of a drug solution by liquid nitrogen, resulting in a modified starting material for homogenization. The organic solvent selected for freeze-drying must have a high freezing point so that it crystallizes fully during lyophilization. The technology works efficiently with thermolabile drugs owing to low temperatures and eliminates organic solvent residues [8,52]. 5. Combinative technology CT is an important approach that includes both pretreatment and a main step as top-down methods. Low-energy ball milling is treated as a pretreatment step followed by HPH. Milling produces a nanosuspension with particles of 600e1500 nm, which are further processed by homogenization. Usually, a low homogenization pressure (100e500 bar) is applied, yielding small drug particles compared with when the operating pressure is high (1500 bar) after ball milling. CT has the advantages of not having to use an organic solvent, reducing homogenization, and needing less production time. The major drawback is a larger particle size compared with other combination techniques [8]. Table 3.1 provides an overview of the chapter. TABLE 3.1 Synthesis approaches

Overview of synthesis approaches to nanocrystals. Advantages

Disadvantages

References

Simple process, no use of organic solvent, low batch-tobatch variation, easy to handle

High grinding time from hours to days, amorphous particles increase production heat, contamination from milling media, low stability

[38,51,53,54,55]

High-pressure Easy to scale up, no use of homogenization organic solvent, generates less impurities than WBM

High-energy input, high homogenization pressure, large production time, high homogenization cycles

[38,51,53,54,55,56]

Top-down approach WBM

Bottom-down approach Precipitation

No high-energy input, scalable, Difficult to control particle growth, involves low cost of equipment high amount of organic solvent, organic solvent residue, stability and crystallinity issues

[38,51,55,56,57]

Combination approaches

Reduces processing time, smaller particle size, stable nanosuspensions

[54,55,56]

Pretreatment step may increase complexity and cost of process

WBM, wet bead milling.

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5. Discussion The bottom-up approach has the advantages of low energy consumption, the involvement of simple instruments, cost-effectiveness, and the ability to work at low temperatures. However, it has not been established as a successful approach on the commercial front. The topdown approach has been universally accepted for large-scale production, but it has a major drawback in terms of particle size reduction efficiency, which creates the urgent demand for alternate approaches. For the large-scale production of nanocrystals, a combination approach is preferred and should be explored more than standard (bottom-up and top-down) processes. Moreover, this could be helpful for tackling the limitations of conventional techniques used to produce nanocrystals on a commercial scale.

List of abbreviations CT Combinative technology HPH High-pressure homogenization RESS-SC Rapid exchange of supercritical solution solid co-solvent RESOLV Rapid exchange of supercritical solvent in liquid solvent RESS Rapid expansion of supercritical solvent SAS Supercritical antisolvent SCF Supercritical fluid WBM Wet bead milling

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Green synthesized nanofunctionalized material Suganthi Nachimuthu1, S. Thangavel2 and Karthik Kannan3 1

Department of Physics, Government Arts College (Affiliated to Bharathidasan University), Kulithalai, Karur, Tamilnadu, India; 2PG and Research Department of Physics, Jairams Arts and Science College (Affiliated to Bharathidasan University), Karur, Tamilnadu, India; 3School of Advanced Materials Science and Engineering, Kumoh National Institute of Technology, Gyeongbuk, Republic of Korea

1. Introduction 1.1 Nano-synthesized material Green synthesis is a field that uses nontoxic and safe reagents to provide economic and environmental benefits. It is environmentally friendly and biologically safe and an alternative to chemical and physical approaches. Nanoparticles (NPs) have a huge influence on the morphology of embedded particles, such as size, physicochemical properties, and shape. Metal oxides have been extensively studied owing to the wide variation of structure, morphology, and size with functional features revealed in their NPs. The bottom-up approach chemically and biologically synthesized NPs via self-building atoms into novel nuclei that produced nanosized particles, including chemical reduction, electrochemical, and sonodecomposition [1]. In most cases, NPs are biosynthesized through microbial or plant extracts that convert metal particles to NPs via the catalyst produced by the cells themselves. The key constituents in a chemical method are metal precursors, stabilizers, and reducing elements (both inorganic and organic). Sodium citrate, ascorbic acid, sodium borohydride (NaBH4), polyol process, Tollens’ reagent, and polyethylene glycol are used as a reducing agent [2]. Therefore, there is a clear need for alternative, economical, safe, and eco-friendly NP manufacturing technologies. The reference to more green, safe, and biologically friendly chemicals and protocols in the preparation related to NP synthesis reduces costs and minimizes the disposal of harmful substances [3].

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1.2 Green synthesis of nanomaterial Green synthesis is necessary to prevent the creation of unsolicited or unsafe outcomes by creating reliable, sustainable, and environmentally friendly synthetic procedures. The green synthesis of NPs is a facile, economical, relatively reproducible technique that produces longer, more stable materials than others. Therefore, NP production must be cost-effective and environmentally sustainable and be widely recognized by society [4]. Extensive research has been conducted on biological sources such as bacteria, fungi, yeasts, and plants. In addition, inorganic metal ions have been converted into metal NPs. Moreover, ecologically friendly methods in chemistry and chemical technology are indispensable because of global issues related to environmental pollution. An important factor is ensuring the environmental friendliness of the final product and the use of sustainable processes. To overcome shortcomings, a green approach to NPs has emerged.

2. Basic mechanism of green synthesis There are three mechanisms for preparing metal NPs in plants and plant extracts: (1) Activation stage: This stage emphasis metal ion reduction and the nucleation of reduced metal atoms. Metal ions change from a monovalent or divalent oxidation state to a zero state, resulting in the nucleation of reduced metal atoms [5]. (2) Growth stage: Adjacent small NPs spontaneously fuse with large particles by the Ostwald ripening process. As the growth phase increases, the NPs agglomerate into morphologies such as nanocubes, nanospheres, nanotriangles, nanohexagons, nanopentagons, nanorods, nanowires, nanotubes, and many other irregularly shaped NPs [6]. (3) At the end stage, NPs secure the utmost dynamically beneficent conformations, and the ability of the plant extract to sustain metal NPs controls the definitive shape of the NPs [7]. Fig. 4.1 shows the process of NP formation.

FIGURE 4.1 Nanoparticle formation mechanisms.

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3. Various methods for green synthesis Physical and chemical methods to synthesize NPs have caused environmental concern as a result of their toxicity. Plant-based NPs synthesis is not a massive procedure. Metal salts are synthesized in plant extracts. The reaction is completed within a few hours at room temperature. The green synthesis of NPs can be obtained from microorganisms, parasites, plants, plant extracts, and so on.

3.1 Biobased (plants) methods 3.1.1 Green synthesis from enzymes The defined structure and usability enzyme pureness cause it is suitable for green synthesis. For example, silver NP processes powerful chemicals in the synthesis of NP. The enzyme is contained in a multilayer polymer membrane collected by electrostatic interaction and developed directly and a green synthesis of dimetal Fe/Pd NPs in the membrane field [8]. Reducing NP with beet juice in the reported method, the authors received a higher size of Ag NPs, which showed higher catalytic action and stability compared with those fabricated with NaBH4 [9]. Au NPs functionalized by redox enzymes act as an electron transducer between the biocatalyst and the electrodes able to be employed in a variety of sensors [10]. 3.1.2 Green synthesis from vitamins Green synthesis of Ag and palladium NPs with different nanostructures were prepared for use in vitamin B2 as reducing and capping compounds. Vitamin B2 has been used as a reducing compound in the preparation of nanowires and nanorods. It is an exclusive technique in the domain of green nanotechnology, for the use of natural substances to advance in this technique [11]. Ascorbic acid (vitamin C) is used as a capping and reducing compound through chitosan as a stabilizer that may bind to metal ions, and the quantity of NPs is determined by the concentration of chitosan exploited [12]. 3.1.3 Microwave-assisted synthesis In contrast with heat treatment, the microwave (MW) method supports uniform heating of precious metals and simple nucleation. A rapid method of NP formation (within seconds) for synthesizing Au, Ag, palladium, and platinum in aqueous media using MW used irradiation at 50 W with red grape pomace and was considered a reducing compound [13]. Kou and Varma reported a facile, environmentally friendly, quick (5-min) method to build Ag NPs by irradiating MW with beet juice as a reducing agent. The fabricated Ag NPs showed good photocatalytic action against the decomposition of methyl orange dyes [14]. 3.1.4 Plants and phytochemicals Metal NPs derived from plant extracts are synthesized from living plants. Plant parts such as roots, leaves, latex, seeds, and stems have been broadly used for metal-based NP preparation. Primary phytochemicals within plants are flavones, terpenoids, ketones, aldehydes, carboxylic acids, and amides. These phytochemicals are responsible for the bioreduction of NPs [15].

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4. Green synthesized nano-functionalized material

Also, several features of solution mixes, including the plant extract intensity, metal salt strength, reaction solution pH, and other reaction environments such as the reaction time and temperature, have a significant effect on the size, superiority, and morphology [16]. It is economical, environmentally friendly, facile, and rather reproducibility. These features enhance the future eco-friendly plants biosynthesize metallic NPs which are used as refinement appliances [17].

3.2 Microorganism The synthesis of NPs by microorganisms is more effective over their protection. The resistance offered by bacterial cells to reactive ions in the synthesis of NPs. To combat cell death, its cell technology supports converting reactive ions into stable atoms (i.e., the NPs of the corresponding ions). This characteristic of bacteria is used in the biosynthesis of NPs. The formation of high-intensity NPs may lead to cell destruction. Microorganisms reside in ambient conditions in an environment where parameters such as pH, temperature, and pressure change. However, this is restricted because of the influence of the reaction time that occurs among metal NPs and the microorganisms that might ultimately destroy cell structures [18]. 3.2.1 Bacteria and actinomycetes Bacterial species are used as templates for biologically derived NPs because they are amenable to mass growth and rapidly reduce metal NPs, which are relatively active against commercially available catalysts for chemical synthesis. Prokaryotic bacteria and actinomycetes are widely employed in the fabrication of metal and metal oxide NPs. The use of bacteria to prepare metal NPs has the advantage of controlling the size of NP by modeling, and reducing Pd using enzymes prevents the use of poisonous chemicals as capping compounds [19]. Besides, this method operates at an ambient temperature, making the NP synthesis process economically attractive. The ability to synthesize NP is also found in other gram-negative bacteria such as Shewanella oneidensis, Escherichia coli, and Pseudomonas putida, and positive bacteria such as Bacillus sphaericus and Arthrobacter oxydans [20]. 3.2.2 Yeasts and fungi The synthesis of NPs by fungi is common to obtain NPs because the biomass is easily processed and affordable, and secretion of extracellular enzymes is effective and indicates the wide-ranging creation of enzymes [21]. Also, the rate of synthesis for processing all of the biomass produced is slow. The fungal-facilitated preparation of metal/metal oxide NPs is an effective procedure for obtaining monodisperse NPs with a well-defined morphology. Because of the presence of various intracellular enzymes, they perform as optimal biological factors for producing metal NPs and metal oxides. Competent fungi can synthesize more NPs than bacteria [15]. Also, fungi have numerous advantages over other organisms because of the existence of enzymes, proteins, or reducing agents on the cell surface. A mechanism such as enzymatic reduction in the cell wall or the fungal cell precedes the creation of metallic NPs. Several fungal species are used to synthesize metal and metal oxide NPs, including silver, gold, titanium dioxide, and zinc oxide [22].

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3.2.3 Algae Algae are used for NP synthesis with various properties in different applications. Singaravelu et al. studied Sargassum wightii to prepare gold NPs [23]. Cyanobacteria and eukaryotic green deposits are appropriate materials for the biorecovery of metal from a liquid state [24]. Uma Suganya et al. reviewed green synthesized Au metal NPs through the exploitation of blue-green development. Au NPs were produced by reducing Au3þ particles of chloroauric destructive to Au0 with Streptomyces platensis protein [25].

3.3 Waste Agricultural waste may be used for NP synthesis, such as cocos nucifera coir, corncob, fruit seeds, and peels. Agricultural waste with biomolecules such as flavonoids, phenols, and proteins functions as reducing agents for NP preparation [26]. Extracts of food waste are commonly used as reducing and stabilizing compounds for NP preparation with various activities including pesticides, antioxidants, antibacterial agents, and catalysts for cytotoxicity against cancer cells. This method is economical and can generate valuable materials by nanotechnology.

3.4 Solvent system-based green synthesis Solvents, whether green or not, are the main components of synthesis. The water is always the ideal solvent. According to Sheldon, “the best solvent is not a solvent, but water is ideal if a solvent is needed” [27]. At the beginning of nanoscience and nanotechnology, water is used as a solvent to synthesize NPs such as Au and Ag NPs, which are synthesized at ambient temperature with functional molecules such as gallic acid [28]. Ionic and supercritical liquids are also the best solvent. Ionic liquid (IL) consists of ions with melting points less than 100 C. It is also known as room temperature ILs. IL can be used as a solvent for metal NPs such as Au, Ag, Al, Te, Ru, Ir, and Pt [15]. ILs can perform as reducing as well as protective compounds in NP preparation. Owing to its ionic nature, it performs as a catalyst [29]. Bussamara et al. investigated the preparation of manganese oxide (Mn3O4) NPs via imidazolium ILs and oleyl amine. Lazarus et al. prepared Ag NPs in BmimBF4, which are smaller isotropic spheres with a high degree anisotropic hexagonal structured formation [30,31]. For instance, 1-butyl-3-methylmidazole (Bmim) hexafluorophosphate (PF6) is anisotropic; especially its tetrafluoroborate analog (BF4) is hydrophilic. These perform like ILs and as catalysts [29].

4. Factors affecting green synthesis In NP formation, the metal ion reduction remains affected by features such as the pH of the solution mixture, preparation temperature, reaction time, metal ion intensity, and potentiality.

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4. Green synthesized nano-functionalized material

4.1 Solution mixture pH The plant extract’s pH value has a significant effect on the creation of NPs [32]. Fluctuations in pH lead to changes in the charge of phytochemicals that exist in the extract. They also affect the potential for binding and reducing metal cations and anions in NP synthesis. Changing the pH causes charge conversion in plant biotransforms, which contributes to changing the procedure to chelate and decompose metal ions. This can alter the shape and size, including the production of synthesized NPs. For example, in the extract of Avena sativa (normal oats), more fine-grained NPs are created at pH 3.0 and 4.0 and higher accumulated particles are detected at pH 2.0. The reducing action of reducing atoms as well as the main nucleation occurs at highly acidic pH values. Hexagonal and triangular gold nanoplates from pear extracts and silver NPs from Curcuma longa (turmeric) were synthesized at an alkaline pH. The extracts were more negatively charged to bind and reduce gold and silver ions efficiently [33].

4.2 Growth temperature NPs synthesized by plant extracts are also affected by temperature [34]. Practically, increasing the temperature raises the reaction rate and the efficiency of the NP preparation. Also, crystalline particles occur at temperatures above room temperature. Silver nanotubes are formed primarily at room temperature in Cassia fistula (golden rain) extract and hyperspherical NPs govern at temperatures beyond 60 C [35]. Moreover, higher temperatures can accelerate nucleation, impairing the secondary reduction process and subsequent metal condensation on the NP surface [34]. Faster growth dynamics occur at higher temperatures, making defect rates occur simultaneously and affecting crystal quality.

4.3 Electrochemical potential of a metal ion The efficacy of metal NP preparation is governed by the potential of the ions. Therefore, the ability of plant extracts can efficiently reduce metal ions [36]. An alternative significant factor for NP characterization is the surface charge. It influences the interaction of NPs with biological nature and electrostatic interaction through the bioactive complexes of plants, algae, fungi, and bacteria.

4.4 Concentration The presence of microorganisms in the reaction solution hinders aggregation and raises the number of nucleation sites, which also reduces the assembly of metal ions. Adding a plant extract to a small space more rapidly promotes binding and reduces metal ion reduction near the surface of microorganisms. For example, metal ions formed by viral particles cause metallization of viral particles and the formation of nanowires for the tobacco mosaic virus, which then reduces the rate of formation of “free” NPs [32].

4.5 Reaction time Nucleation time is also important for size control and size distribution, but the shorter the nucleation time, the better to limit the size of the NPs, because the coarsening effect is time-

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dependent. For instance, it is possible to change the shape and size of the generated NP by changing the amino acid sequence. It can change the kinetics of the NP formation reaction [32]. However, the interplay of polyphenols with NPs is less clear because of the contribution of various biomolecules that cause reducing agents and capping agents. It needs to work on optimizing solvent ratios, reaction times, temperatures, pH, and mixing ratios of the plant extracts to the metal solutions.

5. Application of green synthesized nano-functionalized material 5.1 Biomedical field Dentistry: Silver NPs (Ag-NP) are used for dental instruments and specimens. The addition of Ag-NP to orthodontic adhesives can increase the shifting nature of orthodontic cement by increasing its validation in genetics. Ag NPs are widely use in the medical field for infectious diseases. Dental caries, known as tooth decay, are produced by acidogenic species of bacteria such as Streptococcus mutans, Lactobacillus, and Actinomyces. Drug-mixed Ag NPs were estimated compared with dental caries and periodontal illness-producing microorganisms such as S. mutans, Staphylococcus aureus, Lactobacillus acidophilus, Micrococcus luteus, and Candida albicans [37]. Drug delivery: The green synthesis of NP has been as stable after it has an aquatic nature [38]. Owing to their small size, the NPs enter small capillaries and removed by cells, allowing the drug to accumulate in the target area effectively. Au NP’s wide range of features, including excellent optical and physicochemical, and nontoxicity, cause nano-coercing in drug delivery systems. Advantages of using ZnO NP for drug delivery are that because of their small size, NPs can enter small capillaries and become attracted by cells, permitting the drug onto the target site. Moreover, the biosynthesized NPs permits long-term liberation of the drug into the task area [39]. Dissemination over the egg membrane was examined; the existence of ZnO NP contained in the drug strongly affected the biological membrane (Fig. 4.2) [40]. Optical imaging: Fluorescent carbon dots synthesized by low-temperature carbonization and easy filtration employ watermelon skin, a reproductive raw material that is a carbon resource. This simple method creates a wide-ranging formation of aqueous carbon dot dispersal with no posttechnique. The fabricated carbon dots have a small particle size (w2.0 nm), are extremely soluble in water, and have great luminous efficiency, which makes them ideal fluorescent probes for cell imaging. HeLa cells reacting with carbon dots at 37 C for 3 h under stimulation at 488 nm show a bright luminescence of C-dots in the cell cytoplasm region. This showed that carbon dots have excellent biocompatibility as a bioimaging agent and can be employed like an attractive optical probe [41]. Biomarking: In the biomedical field, NPs are used as biolabels. Immobilization and labeling of biomolecules on NPs to produce hybrid molecules were analyzed. This could be achieved in various ways, including specific recognition, coadhesion, physical adsorption, and electrostatic bonding [42]. Gold NPs are engaged in in vivo gene therapy, protein, nucleic acid delivery, and targeting [43]. ZnO NPs help maintain the biological activity of immobilized biomolecules, provide increased sensitivity, and ensure labeling biomarker detection (Table 4.1).

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FIGURE 4.2 Nanoparticle in targeting and drug delivery.

TABLE 4.1

Overview of biological application of biosynthesized NPs.

Nanomaterial

Reducing agent

Synthesis method

Morphology

Application

Reference

Ag

Justicia glauca

Green method

Spherical

Antimicrobial activities for dental caries and periodontal illness

[38]

Ag

Aloe arborescens

Sunlight mediated

Spherical

Cellular imaging and bactericidal mechanism

[43]

ZnO

Ocimum tenuiflorum leaf extract

Green method

Spherical

Nonenzymatic glucose biosensor

[44]

N-doped carbon dots

L-Ascorbic acid and b-alanine

Microwaveassisted green synthesis

Spherical

Bioimaging of Madin-Darby canine kidney cells (MDCK) and HeLa cells.

[45]

5.2 Electronic devices 5.2.1 Sensors Biosensor fabrication is also a nanotechnology in the biomedical sciences that contributes to the recognition of biological analytes. Mishra and Rajakumari in 2019 fabricated nanosized particles for toxic gas sensors. The incorporation of nanomaterials into biosensors has promoted wearable biochips, which could identify biological analytes and diagnose diseases (Chandra and Segal 2016). The interface between green-synthesized NPs/quantum dots and the analyte triggers a variety of sensory methods such as colorimetric, fluorescence, electrochemical, and surface-enhanced scattering. Surface plasmon resonance (SPR) is found in neem leaf extracts that contains a high intensity of diterpenoids. The prepared Ag NPs grow in a spherical shape with excellent stability.

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References

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[62] S.M. Dizaj, F. Lotfipour, M. Barzegar-Jalali, M.H. Zarrintan, K. Adibkia, Antimicrobial activity of the metals and metal oxide nanoparticles, Mater. Sci. Eng. C 44 (2014) 278 284. [63] C. Ramteke, T. Chakrabarti, B.K. Sarangi, R.-A. Pandey, Synthesis of silver nanoparticles from the aqueous extract of leaves of ocimum sanctum for enhanced antibacterial activity, J. Chem. 2013 (2013) 1 7. [64] A. Verma, M.S. Mehata, Controllable synthesis of silver nanoparticles using neem leaves and their antimicrobial activity, J. Radiat. Res. Appl. Sci. 9 (1) (2016) 109 115. [65] P. Velmurugan, S.C. Hong, A. Aravinthan, Comparison of the physical characteristics of green-synthesized and commercial silver nanoparticles: evaluation of antimicrobial and cytotoxic effects, Arab. J. Sci. Eng. 42 (2017) 201 208. [66] S. Zinjarde, Bio-inspired nanomaterials and their applications as antimicrobial agents, Chronicles Young Sci. 3 (1) (2012) 74 81. [67] Y. Cui, Y. Zhao, Y. Tian, W. Zhang, X. Lü, X. Jiang, The molecular mechanism of action of bactericidal gold nanoparticles on Escherichia coli, Biomaterials 33 (7) (2012) 2327 2333. [68] N. Suganthi, S. Thangavel, K. Karthik, Hibiscus subdariffa leaf extract mediated 2-D fern-like ZnO/TiO2 hierarchical nanoleaf for photocatalytic degradation, Flat Chem. 24 (2020) 100197. [69] N. Suganthi, K. Pushpanathan, Photocatalytic degradation and antimicrobial activity of transition metal doped mesoporous ZnS nanoparticles, Int. J. Environ. Sci. Technol. 16 (2019) 3375 3388. [70] N. Suganthi, K. Pushpanathan, Photocatalytic degradation and ferromagnetism in mesoporous La doped ZnS nanoparticles, J. Mater. Sci. Mater. Electron. 29 (2018) 13970 13983. [71] N. Suganthi, K. Pushpanathan, Mesoporous ZnS: Ce nanoparticles for photocatalytic organic pollutant treatment, J. Inorg. Organomet. Polym. Mater. 29 (4) (2019) 1141 1153. [72] A. Noblecourt, G. Christophe, C. Larroche, G. Santa-Catalina, E. Trably, P. Fontanille, High hydrogen production rate in a submerged membrane anaerobic bioreactor, Int. J. Hydrogen Energy 42 (2017) 24656 24666. [73] J.D. Holladay, J. Hu, D.L. King, Y. Wang, An overview of hydrogen production technologies, Catal. Today 139 (2009) 244 260. [74] M.L. Chong, V. Sabaratnam, Y. Shirai, M.A. Hassan, Biohydrogen production from biomass and industrial waste by dark fermentation, Int. J. Hydrogen Energy 34 (2009) 3277 3287. [75] B.F. Liu, N.Q. Ren, J. Ding, G.J. Xie, W.Q. Guo, The effect of Ni2þ, Fe2þ and Mg2þ concentration on photohydrogen production by Rhodopseudomonas faecalis RLD-53, Int. J. Hydrogen Energy 34 (2009) 721 726. [76] S. Mohanraj, S. Kodhaiyolii, M. Rengasamy, V. Pugalenthi, Green synthesized iron oxide nanoparticles effect on fermentative hydrogen production by Clostridium acetobutylicum, Appl. Biochem. Biotechnol. 173 (2014) 318 331. [77] Y. Goto, T. Hisatomi, Q. Wang, T. Higashi, K. Ishikiriyama, T. Maeda, Y. Sakata, S. Okunaka, H. Tokudome, M. Katayama, et al., A particulate photocatalyst water-splitting panel for large-scale solar hydrogen generation, Joule 2 (2018) 509 520. [78] S. Sekar, S. Lee, P. Vijayarengan, K.M. Kalirajan, T. Santhakumar, S. Sekar, S. Sadhasivam, Upcycling of wastewater via effective photocatalytic hydrogen production using MnO2 nanoparticles decorated activated carbon nanoflakes, Nanomaterials 10 (8) (2020) 1610. [79] M. Kubo, R. Mano, M. Kojima, K. Naniwa, Y. Daiko, S. Honda, E. Ionescu, S. Bernard, R. Riedel, Y. Iwamoto, Hydrogen selective SiCH inorganic organic hybrid/g-Al2O3 composite membranes, Membranes 10 (10) (2020) 258. [80] Y. Abdallah, S.O. Ogunyemi, A. Abdelazez, M. Zhang, X. Hong, E. Ibrahim, A. Hossain, H. Fouad, B. Li, J. Chen, The green synthesis of MgO nano-flowers using Rosmarinus officinalis L. (Rosemary) and the antibacterial activities against Xanthomonas oryzae pv. Oryzae, Biomed. Res. Int. 2019 (2019) 5620989. [81] R. Heydari, M. Rashidipour, Green synthesis of silver nanoparticles using extract of Oak fruit hull (Jaft): synthesis and in vitro cytotoxic effect on MCF-7 cells, Int. J. Breast Cancer (2015) 1 7. [82] J. Mei, H. Chen, Q. Liao, A.-S. Nizami, A. Xia, Y. Huang, X. Zhu, X. Zhu, Effects of operational parameters on biofilm formation of mixed bacteria for hydrogen fermentation, Sustainability 12 (2020) 8863.

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C H A P T E R

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Biological and chemical impact of nanocellulose: current understanding Pragnesh N. Dave1 and Shalini Chaturvedi2 1

Department of Chemistry, Sardar Patel University, Anand, Gujarat, India; 2Department of Chemistry, Silver Oak Institute of Science, Silver Oak University, Ahmedabad, Gujarat, India

1. History of nanocellulose Since the Chinese discovered how to make paper in 150 BCE, cellulose scientists have understood that cellulose in trees and plants is composed of millimeter-size fibers made of repeatedly smaller macrofibers and microfibers of microfibrils of nanometer (10 7 to 10 9 m) dimensions, which form the basic structure of cellulose from all sources. Investigators were persuaded that isolated nanosized microfibrils would have an enormous surface areas and tough bonding, ensuing in novel products with immensely better power and functioning characteristics.

2. Nanocellulose: descriptions, use, and applications Cellulose (Latin: rich in small cells) is a biopolymer found naturally in, for instance, plant cells such as wood and cotton. It is the most rich polymer in the environment and is the main component in the cell wall of plants and trees. Cotton have the maximum cellulose content of the plants, with about 90% cellulose, compared with wood, which has about 40%e50% cellulose content, or bast fibers such as hemp, flax, or ramie, which have about 70%e80% cellulose content [1e3]. Other than wood and plants, cellulose can be found in various bacterial species, algae, and tunicates, a sea animal that consists of proteins and carbohydrates. The annual worldwide production of lignocellulosic biomass is estimated to be approximately 1.3  1010 mt, which can be considered one of the most abundant biopolymers available for reinforcing composites [4]. Nanotechnology has gained huge interest in many industries, and nanotechnology has opened up for many possibilities, such as in the forest industry and cellulose-based products.

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5. Biological and chemical impact of nanocellulose: current understanding

Nanotechnology is defined as the understanding and control of matter with at least one dimension measuring from 1 to 100 nm. By mechanical treatment or chemical modifications on cellulose pulp, nanometer-sized cellulose such as cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs) can be produced. Nanocellulose has extraordinary properties compared with bulk material as well as materials such as Kevlar, carbon fiber, or stainless steel [5,6]. Nanocellulose is not yet a fully commercial product, but the first factory for the production and disposal of CNC opened in 2012 by CelluForce in Canada, which produces about 1 ton/day of CNC. There are also some pilot plants for nanocellulose production located all over the world, and one of the first pilot plants for nanocellulose was opened by Innventia in Sweden in 2011. The first pilot plant in the United States opened in 2012 in Madison and is the country’s leading producer of nanocellulose materials. They produce both CNCs and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-based CNFs. The aim of the pilot plant is to aid the commercialization of nanocellulose materials by providing researchers and early adopters in the area with working quantities of nanocellulose. Nanocellulose refers to nanostructured cellulose, which consists of C6H10O5. Because cellulose is an abundant polymer in nature, large quantities of nanocellulose can be manufactured cost-effectively. Nontoxic and lightweight properties make it easy to carry, so it can be used in applications that require mobility. High tensile, stiffness, and electrical conductivity expand its use through electrical and mechanical applications. Unique properties depending on the type of nanocellulose also exist. There are three types: CNC, cellulose nanofibers (CNF), and bacterial nanocellulose (BNC). The first type of nanocellulose is CNC. Developments in applications show that CNCs have unique specialities for improving the mechanical properties of nanocomposites such as electrospun nanocomposite fibers and mats and nanocomposite hydrogels. Numerous nanocomposite hydrogels reinforced with CNCs can be designed to be sensitive in high temperature, pH, and salt to control drug delivery. In addition, specific applications such as energy-related materials, sensors, photonics, and barrier films can be developed by using CNC-reinforced nanocomposite fibers. For example, Park N. created electroluminescent nanocellulose paper in 2017; one can adjust the color by changing the frequency of the electrical current (Fig. 5.1). The second type of nanocellulose is cellulose nanofibers, which consist of long and thin fibers at the nanometer scale. They form a network with not only crystalline but also amorphous regions. In water, cellulose nanofibers exhibit viscous characteristics. Furthermore, they share some properties with CNC, such as light weight, tensile strength, stiffness, and barrier films. They also have applications in foods, medicine, cosmetics, and health care. As an example of their application, Nippon Paper Group commercialized effective antibacterial and deodorant sheets using CNF with the TEMPO catalytic oxidation method.

2.1 Properties of nanocellulose Nanocellulose is a unique material because of its inherent properties of a high mechanical strength, high surface area, interesting optical and rheological properties, and ease of surface modification.

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FIGURE 5.1 Transmission electron microscopy images of nanocrystalline cellulose. Original magnifications: (A) 3,150,000, (B) 3,100,000. From https://www.researchgate.net/publication/278724020_Nanocrystalline_Cellulose_ Morphological_Physical_and_Mechanical_Properties.

Theoretically, crystalline regions of cellulose have a tensile strength in the range of 50e100 GPa [7]. This is stronger than E-glass as well as Kevlar, which are 3400 and 3000 MPa, respectively [8]. The strongly interacting surface hydroxyl group on nanocellulose contributes to self-association. This property makes nanocellulose a good reinforcing material in composite matrices for the formation of load-bearing percolating architectures within a host polymer matrix. Stress transfer is due to hydrogen-bonding among the nanowhiskers. Besides being stronger than glass, CNCs possess birefringent behavior that can exhibit a liquid crystalline optical property. This liquid crystalline nature can find applications in security paper. Nanocellulose also shows shear thinning and an anomalous manner, which are useful for rheology properties.

2.2 Morphology The morphology of nanocellulose is distinctive for CNC and CNF. Table 5.1 shows the reported morphology of nanocellulose obtained from various sources and by different preparation methods.

2.3 Bacterial nanocellulose Low-cost BNC for enhanced production from agroindustrial waste has been investigated [16]. Owing to green processing, low production costs, elevated mechanical properties,

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TABLE 5.1

Morphology of nanocellulose from different sources and preparation methods [9].

Source

Method of preparation

Width

Length

References

Wood pulp

Acid hydrolysis

5.7e10.7

152e238

[10]

Cotton

Acid hydrolysis

7

177e390

[11]

Rice straw

Acid hydrolysis

5e30

117e270

[12]

Wood pulp

High-pressure homogenization

10e100

e

[13]

Cotton

Grinding

20e90

e

[14]

Kenaf

High-pressure homogenization

10e90

e

[15]

hydrophilicity, excellent biocompatibility, and biodegradability, BNC has earned increasing global interest because of its remarkable physical and chemical properties [17,18]. Bacterial nanocellulose (BNC) production was reported to produce nanocellulose extracellularly by certain gram-negative nonpathogenic bacterial genera such as Xanthococcus, Rhizobium azotobacter, Aerobacter, Pseudomonas, and Alcaligenes [17]. BNC is produced by a two-step process: (1) polymerization and (2) crystallization (Fig. 5.2). The glucose residues polymerize to b-1,4 glucan linear chains in the bacterial cytoplasm, where they are extracellularly secreted. The developed chains are then crystallized to microfibrils, and then certain numbers of microfibrils consolidate to materialize a highly pure three-dimensional porous network of entangled nanoribbons 20e60 nm wide [19]. After incubation for 168 h, the highest BNC yield was perceived on a molasses medium, recording 3.9 g L 1 with an initial concentration of (v/v) 10%. Compared with plant cellulose, BNC is grown in a clean form and is free of lignin, pectin, and hemicellulose. The ultrafine structure of BNC has much higher advantages such as a higher liquid absorption capacity, crystallinity, a higher specific surface area, a higher degree of polymerization, and higher mechanical properties, which make it a better option for the plant cellulose in loads of applications [19,20]. The ease of BNC for modification allows it to be highly finer compared with cellulose of plant origin. In addition, BNC could be fashioned through the fermentation stage to plan tubes, spheres, or membranes according to the application requirements [18]. BNC synthesis by K. saccharivorans MD1 was investigated using the waste of palm date, fig, and sugarcane molasses along with glucose on Hestrin-Schramm (HS) medium as a control [16]. The physicochemical characteristics of BNC sheets were studied by adopting fieldemission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) analysis. The FESEM characterization revealed no impact of the waste on either the fiber diameter or the branching scheme, whereas the AFM depicted a BNC film in which minimal roughness was generated using date waste. Furthermore, a high crystallinity index was estimated by XRD up to 94% for date waste-derived BNC, whereas the FTIR analyses exhibited similar profiles for all BNC films.

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FIGURE 5.2 Schematic of bacterial nanocellulose (BNC) biosynthesis by Komagataeibacter saccharivorans MD1. HS, Hestrin-Schramm. Adapted from D. Abol-Fotouh, M.A. Hassan, S. Hassan, A. Roig, M.S. Azab, A.E.H.B. Kashyout, Sci. Rep. 10 (2020) 3491, https://doi.org/10.1038/s41598-020-60315-9.

In addition, the mechanical characteristics and water-holding capacity of the produced BNCs were studied. Our findings substantiated that expensive substrates could be exchanged by agroindustrial waste for BNC production, conserving its remarkable physical and microstructural properties.

2.4 Applications of nanocellulose Cellulose nanocomposites (nanocellulose) is supposed to be a substitute for man-made materials in environmentally friendly resources and is an addition to entirely new types of biomaterials. Potentical applications of nanocellulose are listed in Table 5.2. Table 5.2 shows recognized applications of nanocellulose based on high and low volumes and novel and emerging applications [9]. Cellulose nanocomposites are used in the automotive industry, medicine, electronics, packaging, construction, and wastewater treatment applications. Sensors and electronics niche applications may yet not be in demand up because further research is still desirable to expand these.

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5. Biological and chemical impact of nanocellulose: current understanding

Nanocellulose applications [9].

High-volume applications Low-volume applications

Novel and emerging applications

Paper coatings

Paintdarchitectural

Reinforcement fiberdconstruction

Paper filler

Paintdspecial purpose

Sensorsdmedical, environment, industrial

Automotive interior

Paintdoriginal equipment manufacturer (OEM) applications

Water filtration

Packaging coatings

Aerogels for oil and gas industry

Air filtration

Packaging filler

Insulation

Viscosity modifiers

Replacementdplastic packaging

Wallboard facing

Cosmetics

Plastic film replacement

Aerospace structure

Purification

Automotive body

Aerospace interiors

Excipients

Cement

Organic LED

Hygiene and absorbent products

Flexible electronics

Textiles for clothing

Photovoltaics Recyclable electronics Three-dimensional printing Photonic films

3. Summary Because it is renewable and biodegradable and owing to its many interesting and unique characteristics, nanocellulose has much to offer in the near future. Nanocellulose has many impending applications in loads of areas such as in basic products including packaging, cement, paper products, and the automotive industry, as well as in niche products such as flexible electronics and sensors. Turning wood into nanocellulose could create new wealth and revenue for the country. Nanocellulose prepared from wood cellulose has exclusive and gifted properties, such as the aspect ratio, Young’s modulus, and high crystallinity and tensile strengths, which come from the properties of natural wood cellulose microfibrils. A change in processing technique changes the properties of the resulting nanocellulose, which is reflected in the final product. The search for new, efficient, and environmentally friendly pretreatments remains an important objective. Details and a comparative study of three different types of nanocellulose (CNC, CNF, and BC) will determine their respective applications. Despite difficulties in nanocellulose production, it is readily available on the market, allowing use of all of its outstanding properties. Many established as well as proposed methods have emerged in terms of the large-scale production of nanocellulose. Nanocellulose-based materials are carbon-neutral, nontoxic, sustainable, and recyclable. I. Nanomanufacturing: large-scale synthesis of nanocrystals

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References [1] J.S. Han, J.S. Rowell, Chemical composition of fibers, in: R.M. Rowell, R.A. Young, J. Rowell (Eds.), Paper and Composites from Agro-Based Resources, CRCPress, London, 1996, pp. 83e130. [2] V.K. Varshney, S. Naithani, Chemical functionalization of cellulose derived from nonconventional sources, in: S. Kalia, B.S. Kaith, I. Kaur (Eds.), Cellulose Fibers: Bio and Nano-Polymer Composites, Springer, Berlin, 2011, pp. 43e60, https://doi.org/10.1007/978e3e642e17370e7. [3] M. Börjesson, G. Westman, Crystalline NanocellulosedPreparation, Modification, and Properties in Cellulosed Fundamental Aspects and Current Trends (Chapter 7), Intech Publihsers, 2015. [4] G. Saratale, S. Oh, Lignocellulosics to ethanol: the future of the chemical and energy industry, Afr. J. Biotechnol. 11 (2014) 1002e1013. [5] R.J. Moon, A. Martini, J. Nairn, J. Simonsen, J. Youngblood, Cellulose nanomaterials review: structure, properties and nanocomposites, Chem. Soc. Rev. 40 (2011) 3941e3994, https://doi.org/10.1039/c0cs00108b. [6] R.J. Moon, C.R. Frihart, T. Wegner, Nanotechnology applications in the forest products industry, For. Prod. J. 56 (2006) 4e10. [7] S.J. Eichhorn, A. Dufresne, M. Aranguren, N.E. Marcovich, J.R. Capadona, et al., Review: current international research into cellulose nanofibres and nanocomposites, J. Mater. Sci. 45 (2010) 1e33. [8] A. Dufresne, Nanocellulose, from Nature to High Performance Tailored Materials Walter, de Gruyter GmbH, 2012, p. 460. [9] L. Jasmani, W. Thielemans, Preparation of nanocellulose and its potential application, For. Res. Open Access 7 (3) (2018), https://doi.org/10.4172/2168-9776.1000222. [10] L. Jasmani, S. Adnan, Preparation and characterization of nanocrystalline cellulose from Acacia mangium and its reinforcement potential, Carbohydr. Polym. 161 (2017) 166e171. [11] X.M. Dong, J.F. Revol, D.G. Gray, Effect of microcrystallite preparation conditions on the formation of colloid crystals of cellulose, Cellulose 5 (1998) 19e32. [12] P. Lu, Y.L. Hsieh, Preparation and characterization of cellulose nanocrystals from rice straw, Carbohydr. Polym. 87 (2012) 564e573. [13] F.W. Herrick, R.L. Casebier, J.K. Hamilton, K.R. Sandberg, Microfibrillated cellulose: morphology and accessibility, J. Appl. Polym. Sci. Appl. Polym. Symp. 37 (1983) 797e813. [14] T. Taniguchi, K. Okamura, New films produced from microfibrillated natural fibres, Polym. Int. 47 (1998) 291e294. [15] M. Jonoobi, J. Harun, A.P. Mathew, K. Oksman, Mechanical properties of cellulose nanofiber (CNF) reinforced polylactic acid (PLA) prepared by twin screw extrusion, Compos. Sci. Technol. (2010) 1742e1747. [16] D. Abol-Fotouh, M.A. Hassan, S. Hassan, A. Roig, M.S. Azab, A.E.H.B. Kashyout, Sci. Rep. 10 (2020) 3491, https://doi.org/10.1038/s41598-020-60315-9. [17] M. Gao, et al., A natural in situ fabrication method of functional bacterial cellulose using a microorganism, Nat. Commun. 10 (2019) 437, https://doi.org/10.1038/s41467-018-07879-3. [18] H. Ullah, F. Wahid, H.A. Santos, T. Khan, Advances in biomedical and pharmaceutical applications of functional bacterial cellulose-based nanocomposites, Carbohydr. Polym. 150 (2016) 330e352, https://doi.org/10.1016/ j.carbpol.2016.05.029. [19] F.G. Torres, J.J. Arroyo, O.P. Troncoso, Bacterial cellulose nanocomposites: an all-nano type of material, Mater. Sci. Eng.: Chimia 98 (2019) 1277e1293, https://doi.org/10.1016/j.msec.2019.01.064. [20] X. Chen, et al., Recent approaches and future prospects of bacterial cellulose-based electroconductive materials, J. Mater. Sci. 51 (2016) 5573e5588, https://doi.org/10.1007/s10853-016-9899-2.

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S E C T I O N I I

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Recent trends in nanocrystals for pharmaceutical applications Pandey Annu1, 3 and Ayushi Singhal2 1

School of Studies in Environmental Chemistry, Jiwaji University, Gwalior, Madhya Pradesh, India; 2CSIReAdvanced Materials and Process Research Institute, Bhopal, Madhya Pradesh, India; 3Department of Chemistry, Chandigarh University, Mohali, Punjab, India

1. Introduction Applications of nanoscience and technology for working with, analyzing, examining, and managing drug biological system are termed “nanomedicine.” Normal delivery and pharmaceutical, therapeutic, and diagnostic mediators are major concerns of developments in nanomedicine. These include the recognition of specific targets related to definite clinical states and the preference of suitable nanocarriers to attain the necessary responses to reduce side effects [1]. Advances in particle design and formulation of nanotechnology have begun to be marketed for numerous drugs and are creating a greatly advantageous niche in industries. However, several of these advantages are hyped. Nanomaterials have extensive applications and methods in the pharmaceutical sciences. Some additional fields of application of nanotechnology are in drug delivery and diagnostic imaging. Nanomedicines are nanosized materials applied for treatment, analysis, and diagnostics. Nanosized drug delivery in the form of nanoliposomes, dendrimers, fullerenes, nanopores, nanotubes, nanoshells, quantum dots, nanocapsules, nanospheres, nanovaccines, nanocrystals, and so on have prospects for reforming drug delivery systems [2e5]. There has been a considerable research into drug nanocrystal systems as a pharmaceutical approach to hydrophobic or poorly soluble drugs [6]. The pharmaceutical industry has been caught between the downward pressure of prices and increasing costs of successful drug discovery and development. The total expense (approximately $500 million) and time (10e12 years) to develop of a new drug molecule are much higher compared with those required to develop a novel drug delivery system (approximately $50 million and 4e5 years). The pharmaceutical industry is facing challenges such as limited formularies and patent expirations with subsequent entry generic competition and vertical integration. These challenges

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have led the entire industry to focus on designing and developing new and better methods of drug delivery [1,7,8]. Automation of drug discovery by the development of technologies such as computer-aided drug design, screening, and combinatorial chemistry is helpful for a vast number of drug candidates with good efficacy. Problems such as oral absorption owing to poor solubility and dissolution often impede drug development. Low solubility limits the absorption of drugs into intestinal fluid because the intestinal concentration of the drug reaches solubility in the gastrointestinal tract. After intense research, drug nanocrystals have become a real option for pharmaceutical industry to solve challenges related to poorly soluble drug materials. Nanosizing has become the most important drug delivery platform approach to the commercial development of poorly soluble drug molecules [9e11]. Drug nanocrystals are referred to as drug nanoparticles. These nanocrystals are crystalline with a size in the nanometer range. Nanotechnology has affected our lives tremendously in different fields, including medicine and pharmacy. Drug nanocrystals are pure solid drug nanoparticles coated with a stabilizer layer. In some instances, no stabilizers are needed. Commonly, a layer of polymer or surfactant is needed to stabilize the drug nanocrystal against particle aggregation. The stabilizer layer can be made of either only one material or a mixture (i.e., one polymer and one surfactant can be used). The functionality of drug nanocrystals can be achieved by adding some functional linking groups to the stabilizer layer. Nanocrystals are also referred to as solid micelles. The era of drug nanocrystals began in the early 1990s. The first products were quickly launched on the market from 2000 onward. With some exceptions, all marketed products are made for oral administration; they are in dry dosage form and only some products are suspensions. After oral administration, nanocrystals dissolve in the intestinal tract. This transfer of drug material into the nanodimension changes their physical properties. The method was used in pharmaceutics to develop an innovative formulation principle to allow poorly water-soluble drugs to absorb quickly [12]. Nanoscopic crystals of the parent compound with dimensions less than 1 mm are called drug nanocrystals. According to the Noyes-Whitney equation, the reduced size of drug nanocrystals leads to an enhanced surface area, which ultimately increases the dissolution rate and absorption of poorly soluble drugs. Nanotechnology is a revolutionary domain of science. There, scientific prowess and rigor surpass visionary boundaries. Progress in nanoscience and nanotechnology is the outcome of science and technology, overcoming dramatic challenges. The pharmaceutical industry is working on several medicines with different application routes aiming at the higher functionality of these compounds [13]. One application is the development of drug nanocrystals. The use of cosolvents (e.g., water or ethanol) or solubilizing agents (e.g., surfactants such as Cremophor EL) has been exploited to increase the solubility of poorly water-soluble drugs. The use of solvents leads to an increase in side effects or an adverse reaction in the body because of the solubilizing agents or traces of organic solvents. Therefore, there is an urgent need to develop a safe and effective method to increase the solubility and bioavailability of poorly water-soluble drugs. Thus, different chemical and physical modifications have been performed. Changes include salt formation, drug complexation with cyclodextrins or conjugation to dendrimers, and the preparation of drug dispersions in nanocarriers such as self-microemulsifying drug delivery systems, nanoemulsions, or other lipid-based formulations. For example, to increase the bioavailability of paclitaxel, an injectable solution, Taxol, was produced using Cremophor EL as the solubilizing agent. However, adverse effects such as allergic shock caused by Cremophor EL were reported. The pharmaceutical industry

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considered these compounds to be highly risky development candidates. However, owing to their prevalence, industry consensus has shifted from an attitude of avoidance to one of acceptance, and research is increasingly dedicated to solving solubility challenges [14]. Drug nanocrystals can be formed by combining the two techniques. The first process produces drug nanocrystals by precipitating dissolved molecules. This approach is called bottom-up. In this method, the size of particles increases. The group contains processes such as microprecipitation and chemical synthesis. Particle size reduction or comminution comes under the second process type. This approach is called top-down, because the size of existing particles decreases. The third type involves combinations of bottom-up and topdown steps to improve the effectiveness of particle size reduction of single-unit processes [15,16]. The number of nanocrystalline-based products commercially available, together with the increasing amount of scientific research and number of patents on drug nanocrystals for various applications, indicate that pharmaceutical industries have embraced this universal formulation approach, which is expected to advance further in the near future.

2. Production technology There are three main approaches to preparing drug nanocrystals. The first is the top-down method, in which nanosized particles are prepared by diminishing the particle range of a bulk drug in a liquid suspension by applying various types of milling or homogenization techniques (Table 6.1). The top-down approach uses an elevated force to shrink the particle size and can be employed for a broad series of brick dust drugs. This process is also known as highpressure homogenization technology. Another traditional top down technology is milling a drug for particle size diminution [5,17,18]. Two types of the milling method (i.e., dry milling and wet milling). Primarily dry milling had been applied, but it was overtaken by wet milling because it has the improved potential to achieve nanonization. This technology involves a media milling chamber, a dispersion medium (generally water), and an appropriate stabilizer to obtain a reduction in particle size. Wet milling uses both high- and low-energy routes, depending on the characteristics of particles. The second approach is the bottom-up method. Here, nanosized particles are assembled molecule-by-molecule through precipitation, so it is also termed nanoprecipitation. This technique was first established by List and Sucker. The method entails solubilizing a drug in an appropriate solvent followed by precipitation of the suspended drug by adding a nonsolvent, which results in the synthesis of nanocrystals [19e22]. Bottom-up methods have been examined at the laboratory scale, but scaling up is frequently challenging. Disputed is found also caused by complexity in scheming the particle size increasing, pronouncement an appropriate solvent/antisolvent mixture, and the volume and challenging eliminating procedure of solvents. In particular, the solvent/antisolvent procedure requires the consumption of organic solvents because of the poor solubility of drug materials. The most conventional means is to achieve precipitation by adding an antisolvent. However, adding supercritical liquids, eliminating a solvent, or atomizing the liquid have also been done. The liquid atomization method may generate amorphous materials because of tremendously rapid solvent elimination, which can cause stability problems subsequently when the amorphous drug begins to crystallize [23,24]. The third and most advanced

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6. Recent trends in nanocrystals for pharmaceutical applications

Production technology. Techniques

Advantages

Disadvantages

Top-down approach

1. Ball milling a. Dry ball milling b. Wet ball milling (WBM) ➢ Low energy WBM ➢ High energy (HEWBM) 2. High-pressure homogenization (HPH) a. Jet streaming b. Piston-gap homogenization

• Ease of scale-up; little batch-to-batch deviation fine size in final product flexibility in handling quantity • Small amount of energy • Allocate aseptic manufacture • Universally appropriate • Rapid method • Option of water-free manufacture

• • • •

Bottom-up approach

➢ ➢ ➢ ➢

• • • • • • • • • • •

• Engross organic solvents • Bioavailability decreases • Equipment not easily obtainable • May be inappropriate for heat-labile compounds • Agglomeration of minute particles • Residual toxic solvents in end product • Low glass evolution temperature

Antisolvent addition Supercritical fluids Solvent removal Liquid atomization

Combination (i) Preprocess step (sprayapproach drying, precipitation, lyophilization, media milling) (ii) High-energy, top-down process

Manufacture crystalline Easy setup Decline in organic solvents Suspensions can be recycled Regular size distribution Fewer processing steps Takes place at ambient temperatures Small particle size Easy scale-up Increase dissolution rates Badly water-soluble active pharmaceutical ingredients (APIs)

• Achieved small particle size • Prevents procedure-related difficulty such as clogging • Limits final top-down procedure time

Residues Slow process Unstable Prerequisite of micronized drug particles • Consumes high energy; Requires experience in operation

• Complicated procedure • Raises overall prices • Complexity of whole manufacture procedure

approach for preparing drug nanocrystals is the combination of bottom-up and top-down approaches. The combined process uses the bottom-up and top-down processes in sequence. The combination technology offers an effective approach to make nanoparticle sizes though concurrently carried over the lack of different methods, for instance equipment blockage and extensive course times. In common, the combination technology is composed of a pretreatment pace followed by an elevated-energy top-down procedure. Typically, nanocrystals are initially precipitated by bottom-up technology; afterward, they are bypassed throughout a top-down process [25,26]. Most profitable pharmaceutical products are prepared by top-

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3. Characteristics of drug nanocrystals

down technology, typically by milling. Because of these methods, the procedure is repeatable and easily modified at each level. The yield differs for each method depending on the procedure and varieties. In milling processes, if it is a process is batch process, the yield can be considerably high, but the material can be lost on the surface of the beads and the vessel. The entire preparation methods of solid drug centers are enclosed by a stabilizer coat, however depending on the procedure, definite properties, such as particle shape, size, porosity and stage of crystalline, may be changed depending on the selected method and method parameters. The choice of stabilizer should be supported by the drug properties. However, it is also high-quality to be considered for numerous ordinary stabilizers having a number of drug transfer activities [27,28].

3. Characteristics of drug nanocrystals Drug nanocrystals are crystalline nanoparticles with a size range of a few nanometers to 1000 nm. These are 100% APIs, unlike polymeric nanomaterials that contain carrier materials [29]. Drug nanocrystals are designed to improve the bioavailability of drugs. Drug nanocrystals have various advantages. They increase the solubility, permeability, and stability of drugs, deliver the drug directly to the target side, reducing the chances of toxicity, and reduces the dosage of drugs owing to their high efficiency (Table 6.2) [30]. Drug nanocrystals have many special properties that make them an efficient tool in pharmaceuticals; some of them are briefly discussed.

3.1 Enhanced dissolution rate A size reduction of drug crystals results in an enhanced surface area and increased dissolution velocity according to the Noyes-Whitney equation: dX=dt ¼ DA=hD  ðCs  CtÞ

TABLE 6.2

(6.1)

Characteristics of drug nanocrystals.

Property

Small particle size

Large particle size

Size

1e1000 nm

>1000 nm

Surface area

Higher

Lower

Dissolution rate

Higher

Lower

Saturation concentration

Higher

Lower

Bioavailability

Higher

Lower

Adhesiveness to surface or cell

Higher

Lower

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where dX/dt is defined as the dissolution rate, D is the drug diffusion coefficient, A is the dissolution surface area, hD is the diffusion layer thickness, Cs is the saturation solubility for a given medium, and Ct is the drug concentration around nanocrystals at a given time point [31]. Therefore, for drugs with a low dissolution velocity, microionization and further nanoionization can result in an increased surface area, decreased diffusion layer thickness, and increased saturation stability, with the ultimate goal of a rapid dissolution rate [1,32].

3.2 Higher saturation solubility The saturation solubility is a constant value, depending on the compound, dissolution velocity, and temperature conditions. The higher saturation stability concept applies to powders with a size in the micrometer range and above. However, below 1e2 mm, saturation stability also depends on the particle size other than the compound, dissolution velocity, and temperature conditions. The saturation stability increases upon reducing the size of the particle below 1000 nm. The saturation stability can be explained with the help of the Noyes-Whitney equation (Eq. 6.1), which shows that the saturation stability increases upon nanoionization with an increase in dissolution velocity (dX/dt). The diffusional distance or diffusion layer thickness (h) depends on the particle size, which can be explained with the help of the Prandtl equation: hH ¼ KðL 1= 2 = V 1=2Þ

(6.2)

Where hH is the hydrodynamic boundary layer, K is a constant, L is the length of the particle surface, and V is the relative velocity of the flowing liquid surrounding the particle. The decreased particle size leads to reduced thickness of the diffusion layer and increased saturation solubility, owing to which the process of absorption also rises between the gut lumen and blood periphery [33]. The increase in saturation stability can also be explained by the Freundlich-Ostwald equation [1] and Kelvin equation [33]. The Freundlich-Ostwald equation was first developed for liquid droplets in gas phase, but it applies to solid nanoparticles in liquid with a size of approximately 1 mm. When the particle size is below 100 nm, saturation stability increases exponentially [1]. The Kelvin equation describes the vapor pressure of liquid over a curved surface of a liquid droplet; it also explains the relation between the curvature of solid particles in liquid and dissolution pressure. The dissolution pressure increases with increased curvature, which ultimately means the reduced size of particles. As described, the saturation solubility increases with reduced size [33].

3.3 Increased adhesiveness Another important property of drug nanocrystals is adhesiveness. Enhanced adhesiveness is found in nanocrystals compared with microcrystals. Nanocrystals enhance adhesiveness to the gastrointestinal mucosa (mucoadhesive). This mucoadhesive property of drug nanocrystals can be used efficiently to improve the absorption of poorly soluble drugs [32]. To develop and characterize the mucoadhesive nanosuspension of ciprofloxacin, researchers

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incorporated nanosuspensions of ciprofloxacin into a mucoadhesive hydrogel. The formulation showed enhanced physical stability, which can result in prolonged residence in the gastrointestinal tract (GIT) and ultimately increase the absorption of drugs. The prolonged residence time in the GIT may decrease the drug dosage and its dosing frequency [34].

3.4 Prolonged stability Nanosystems should have long-term stability for better in vitro formulation development and performance. Physical stability can degrade as a result of the Ostwald ripening phenomenon. The main characteristic of nanosystems, their small size, is also the limiting factor in formulation development. The enhanced interfacial area owing to the reduced size leads to high interfacial energy. During development of the formulation, particles undergo agglomeration and aggregation through Ostwald ripening. The vitro dissolution process and performance can be affected owing to Ostwald ripening. The stability of nanosystems could be maintained by preventing agglomeration and aggregation. The use of stabilizers in the formulation can prevent agglomeration and aggregation. Commonly used stabilizers are polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), polyethylene glycol, hydroxymethylcellulose, hydroxypropylcellulose, carboxymethylcellulose sodium, D-a-tocopheryl polyethylene glycol succinate, polyethylene oxide, polypropylene oxide, dioctyl sodium sulfosuccinate, and sodium lauryl sulfate [35]. In a study, high-performance liquid chromatography (HPLC) data showed that an aqueous solution of paclitaxel degrades after 48 h at room temperature, and the peaks of the degradation product were visible along with the main peak. On the other hand, paclitaxel nanosuspensions stabilized with poloxamer 188 were stable even after 4 years of storage, and only the main peak occurs without any visible degradation product’s peak and showed >99% recovery [36].

3.5 Enhanced diffusion in mucus layer and improved permeability In a variety of organs such as the GIT, a semipermeable layer surrounds the drug molecule and restricts the movement of drugs. Drug nanocrystals generate higher penetration ability across the mucus layer compared with various bulk drugs [16]. Nanocrystals in the size range of 200e300 nm offer the advantage of enhanced permeability across the skin and mucosal membranes [35]. Nanocrystals improved permeability by forming a reservoir of smaller thickness to release the drug and by using stabilizers, avoiding mucus adhesion and improving contact between the drug and epithelial membrane [36]. Enhanced permeation also depends on the shape of nanocrystals. Different-shaped nanocrystals such as slices, ovals, rods, spheres, needles, granules, and irregular shapes can influence absorption and in vivo performance. In a study, the impact of particle shapes on the oral delivery of drug nanocrystals was studied. The results showed that rod-shaped nanocrystals had the best absorption efficiency and bioavailability (1.44-fold and 1.8-fold higher than that of spherical and flaky nanocrystals, respectively) [37].

4. Stabilization Nanosized drug crystals have remarkable benefits although they often lead to concerns about stability. Nanotechnology has affected our lives tremendously in different fields,

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including medicine and pharmaceuticals. Drug nanocrystals are pure solid drug nanoparticles coated with a stabilizer layer. In some instances, no stabilizers are needed. Most of the time, a layer of polymer or surfactant is needed to stabilize drug nanocrystals against particle aggregation. The stabilizer layer can be made of only one material or a mixture (i.e., one polymer and one surfactant can be used). The functionality of drug nanocrystals can be achieved by adding functional linking groups to the stabilizer layer. The major surface area of nanocrystal consequences in adequately high free energy or surface charge which may lead to agglomeration. But few time minute-sized nanocrystal increase the solubility of the drug ahead of the saturation spot that endorses re-crystallization into bigger size particles also called Ostwald ripening. These processes ultimately lead to the irreversible loss of formulation integrity [38e40]. The significant sign of instability related to drug nanocrystals is an increase in particle size. This growth can be examined by differential light scattering under a diverse set of conditions. Some important characterization techniques are X-rays diffraction (XRD), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and fourier transfer infrared red spectroscopy (FTIR), which are used to observe the stability of nanocrystals. In addition to formulation activities through the shelf life, specific studies should be performed to authenticate the in vivo stability report of nanocrystals. For example, nanocrystals meant for oral delivery should be able to endure the harsh gastrointestinal environment. Similarly, nanocrystals of water-insoluble drugs are inclined to precipitate upon dilution by gastric and additional body fluids subsequent to administration into the body. Formulation-supported approaches have been assumed to confirm such instabilities. The aggregation of nanocrystals can be restrained by surface stabilization, by applying an appropriate amphiphilic stabilizer that combines hydrophilic and hydrophobic qualities in a single functional molecule [41e44]. The hydrophilic group is appropriate for raising the solubility of an inadequately soluble drug whereas the hydrophobic group is in concurrence with increase the stability of the dangled particles in the dispersal medium. Some of the important stabilizers are discussed next.

4.1 Poloxamers Poloxamers are amphiphilic block copolymers prepared by the amalgamation of ethylene oxide and propylene oxide components assembled in an EePeE array. These exist in a variety of grades grown by dissimilar lengths of polymer blocks. They have a flexible variety of purposes in drug delivery because of their numerous consequences including solubility shift, stability impartment, and diminution in protein binding. These are not identified as ultimate stabilizers; however, they are chemosensitive to multiple drug resistance. Poloxamers are harmless excipients and significantly causes insignificant hemolytic reaction therefore, these are popular for delivering drugs throughout the intravenous pathway [45e48].

4.2 Polyvinyl pyrrolidone PVP is prepared by the reaction of acetylene and pyrrolidone pursued by polymerization to change into PVP. It is accessible in diverse thicknesses and has flexible application, from being a binder in tablets and capsules to being a coating in ophthalmic solution and a significant stabilizer in suspensions [49,50]. II. Pharmaceutical industry

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4.3 Polyvinyl alcohol Partly hydrolyzed PVA is a commonly used stabilizer in the pharmaceutical sector. The degree of polymerization and extent of hydrolysis are main factors affecting the solubility of PVA in water. It has been applied to formulate stable nitrendipine nanocrystals formed by precipitation ultrasonication to get better dissolution properties and induce oral bioavailability [51].

4.4 Sulfuric acid monododecyl Sulfuric acid monododecyl ester sodium salts are an anionic surfactant applied extensively as a wetting mediator. They have mild toxic effects such as eye, skin, and stomach irritation. They were used to prepare nanocrystals of herpetrione, a kind of antiviral agent from Herpetospermum caudigerum, by applying high-pressure homogenization followed by cold drying. The characterization results clearly indicated no change in the root behavior of the drug with the use of this as a stabilizer, and it generally raised the oral bioavailability of drugs. It is a widely used option in production techniques that apply a high processing temperature compared with other stabilizers because of its relatively high melting point [52].

4.5 Brij-78 This is a nonionic surfactant consisting of polyoxyethylene alkyl ethers, also known as Cremophor. Brij-78 is employed as an emulsifier, wetting, and permeation-inducing mediator. In a study, it was used as a stabilizer for processing with oridonin to form nanocrystals. It may also cause anaphylactic hypersensitivity reactions [53]. Despite the use of stabilizers and their complex combinations, the total avoidance of crystal formations cannot be achieved in most processes. In liquid dispersion media, the thermodynamics and molecular kinetics speed up. Therefore, nanosized crystals frequently need to be dried and stable to achieve long-term stability. Freezing and spraying are two methods of eliminating liquid-dispersing nanocrystals. The obtained dried crystals can be processed into proper solid dosage types such as tablets or capsules. During this process, one must ensure that quick dissolution properties of the nanocrystal are not affected. For freeze-drying, the variety and quantity of cryoprotectants have a vital role in sustaining the sensitive structural characteristics of nanocrystals. A lack of cryoprotectants causes a nonfrozen liquid microphase to develop in phase partition into an ice and cryoconcentrated solution, leading to the discriminatory segregation of nanocrystals in microsized nonfrozen liquid pockets, and the possibility of particulate aggregation. 4.5.1 Applications of drug nanocrystals Drug nanocrystals are used for various types of target drug delivery by routes of administration such as oral, dermal, intravenous, pulmonary, and ocular (Fig. 6.1) Dermal application. Drug nanocrystals are used to increase the dissolution of poorly soluble drugs and increase the concentration gradient between the dermal formulation and the dermis (skin). By increasing the concentration gradient, the transdermal penetrating power of formulations increases. The first use of the dermal formulation of nanosuspensions started

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6. Recent trends in nanocrystals for pharmaceutical applications

Application of drug nanocrystals.

with the poorly soluble antioxidant rutin, the first product of which launched commercially in Mar. 2007, followed by the nanosuspension of antioxidant hesperidin, launched in 2009. When a rutin nanocrystal formulation was compared with a water-soluble rutin derivative, the concentration of rutin glycoside in cream was 1000-fold higher [54] This is because the increased solubility of poorly soluble drugs increases the concentration gradient between the skin and the formulation, showing increased penetration power. Similarly, the nanocrystal formulation of the antioxidative agent lutein showed saturation stability and permeability of 26.3-fold and 14-fold, respectively, higher than coarse powder. Another example of a pharmaceutical dermal formulation is solid-in-oil diclofenac sodium nanosuspensions. When administered orally, diclofenac causes severe gastric damage. To overcome this problem, diclofenac nanosuspensions were introduced for transdermal delivery. The prepared nanosuspension of diclofenac showed 3.8-fold increased permeability in a Yucatan micropig skin model compared with the surfactant-free control [55,56]. Oral application: Oral administration of a drug is considered to be the first and most important choice because it is inexpensive, safe, convenient, and easy to take. Drug nanocrystals that are available commercially are mostly used for oral delivery. Poorly soluble drugs have many problems such as variable bioavailability of the drug, a delayed onset of action, variability in bioavailability owing to fast and fed conditions, and high dose use. Drug nanocrystals can overcome these limitations because of their high solubility, high dissolution rate, quick onset, and bioadhesion. The increased bioavailability of poorly soluble drugs can be seen by changes in pharmacokinetics data, such as an increased area under the curve (AUC0et), increased maximum plasma concentration (Cmax), and decreased time to achieve maximum plasma concentration (Tmax) [51]. A reversible proton pump inhibitor, revaprazan hydrochloride (RH), a poor soluble drug with low bioavailability, was studied to investigate

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the particle size reduction effect on dissolution and absorption. Results suggested that the RH nanosuspension had an increased dissolution rate compared with its coarse suspension and exhibited a significant increase in AUC0et and Cmax and a decrease in Tmax. The outcomes of the study revealed that nanoionization enhanced the oral bioavailability of RH and increased absorption in the GIT. Similarly, the bioadhesion of drug nanocrystals owing to the adhesion of the drug to the biological mucosa can influence the bioavailability of the drug. The enhanced bioavailability of drugs occurs because of the higher concentration gradient across the membranes and the prolonged residence time in the GIT [26]. Intravenous application: Drug nanocrystals can be injected intravenously because of nanoscale dimensions. Nanocrystals have advantages over other formulation because they are lungs (rce 3.23).

Clofazimine (antimycobacterial)

High-pressure homogenization, lyophilization

Developed nanocrystalline suspension for iv [51] administration was investigated for the eradication of Mycobacterium avium from infected mice. The system was effective in reducing the bacterial load on vital organs of mice owing to enhanced saturation solubility of the drug.

Camptothecin (DNA topoisomerase I inhibitor)

Sonication precipitation method without addition of stabilizer

Particle size, antitumor activity, and cellular toxicity [52] were examined against MCF7 cells on xenografted BALB/c mice. Camptothecin nanocrystals were stable for 6 months with significant tumor suppression activity because the drug concentration was five times higher compared with the drug salt solution.

Bexarotene (antineoplastic)

Microfluidization

Modification of solubility and bioavailability for [53] potent antitumor effects were aimed at developing nanocrystals. The decreased dimension of bexarotene nanocrystals exhibited an improved dissolution rate, solubility, and absorption after iv administration in mice because it bypassed the enterohepatic circulation.

Atovaquone

Nanoprecipitation

The surface of atovaquone nanocrystals was stabilized [54] with Tween 80 and poloxamers (P184 and P334). The coating of apolipoprotein E (apoE) peptides was done to improve cellular uptake in the brain. An in vivo study on a rat coculture model of the bloodebrain barrier revealed no significant difference in cellular uptake and a parasitic effect of apoE-coated nanocrystals compared with bare crystals. (Continued)

V. Drug delivery

162 TABLE 10.3

10. Drug nanocrystals as drug delivery systems

Drug nanocrystals for parenteral applications.dcont’d

Drug

Methodology

Objectives and outcomes

References

Curcumin didecanoate prodrug (CurDD)

Wet ball milling and lyophilization

[55] Oily intramuscular suspensions were designed to investigate the comparative pharmacokinetics of microsuspensions or nanosuspensions on rats. Slower clearance from nanosuspensions was observed compared with microsuspensions, and the former exhibited a higher plasma curcumin concentration (69 ng mL
1) compared with the latter (18.5 ng mL
1). Long-acting antidepressant CurDD nanosuspensions achieved a reversal effect on reserpine-induced hypothermia for 13 days on a single intramuscular dose.

Itraconazole (antifungal)

Microcrystallization

[56] The solubility of itraconazole was modified and its high dose was adjusted because it was troublesome for patients when taken orally. In vivo studies on rats with the developed nanosuspensions showed improved dissolution solubility, a depot effect, and considerable biodistribution (by mononuclear phagocytic system (MPS)) compared with the solution form.

approved non-ionic triblock copolymer, Poloxamers (Pluronic F68, and pluronic127 at concentration 0.2%e0.6%) are extensively applied as surface stabilizers for nanocrystals owing to their satisfactory hydrophilicelipophilic balance that controls crystal growth and enhances the wettability of particles. Several drugs (e.g., budesonide, nimodipine, indomethacin, and paclitaxel nanocrystals) are stabilized with poloxamers [48]. Other stabilizers such as those derived from amino acids (albumin, lysine, transferrin, and leucine), water-soluble vitamin E tocopheryl polyethylene glycol succinate (TPGS), graft copolymer, Soluplus, cellulosebased hydroxy propyl methyl cellulose (HPMC), and protein-based hydrophobins are widely employed for the formulation of nanocrystals for parenteral delivery [46]. Nanocrystal-based suspensions are frequently administered intravenously, which results in them steadily dissolving and circulating consistently, and provides 100% bioavailability without obstructing small capillaries. Such formulations are designed to deliver anticancer agents because the system has the potential to permeate cancerous cells. It has anticancer activity without disturbing surrounding healthy cells compared with traditional therapy. Various paths of internalization are reported for parenterally administered drug nanocrystals: paracellular transport, clathrin-mediated endocytosis, phagocytosis, and pinocytosis. Paclitaxel nanocrystals were developed that have a high permeation and retention effect. However, their distribution in cancer cells (liver, spleen, and brain) was less prominent compared with conventional formulations because of excessive accumulation in the reticuloendothelial system through macrophages [57]. Thus, the size of the nanocrystal has a crucial role in biological activity and toxicity. Another study on paclitaxel nanocrystals with D-Rtocopheryl polyethylene glycol 1000 succinate as the stabilizer exhibited significant therapeutic action owing to the high payload, sustained release, and stability. The surfactant created a sheath around paclitaxel particles, made them stable, enhanced blood circulation, protected them from macrophages, and reversed multidrug resistance. Hence, an improved anticancer effect was seen in conventional Taxol preparations [58]. V. Drug delivery

1. Introduction

163

For improving the absorption of drug nanocrystals, functionalization or surface modification is suggested. PEG, serum albumin, and dextran through physical adsorption are widely applied surface modifiers for drug nanocrystals. These systems enhance phagocytic or macrophage uptake and mean residence time in the blood compared with bare nanocrystals. Shegokar and Singh (2011) studied the effect of surface modifiers on nevirapine. The outcomes revealed the increased phagocytic uptake of PEG-coated nanocrystals, whereas albumin and dextran-coated nanocrystals were readily taken up through macrophages [50]. Nanocrystals are also decorated with cell-specific ligands for augmented cellular uptake at the targeted tissues. Chemically anchored ligands are reversibly adsorbed over stabilized drug nanocrystals and become attached to receptors present on the cell target surface, exhibiting a therapeutic action [59]. Much research has been conducted to understand the mechanisms behind cell ligands at target tissues (liver, brain, spleen, etc.). Serotonin-labeled CdSe nanocrystals were developed to interact with HeLa/HEK-293, antidepressant sensitive serotonin transporters present on humans, and Drosophila. The developed system exhibited a dose-dependent inhibition of 99 mM in humans and 33 mM in Drosophila [60]. Similarly, red blood cells (RBC) membrane-coated drug nanocrystals (RBC-NCs) were developed that possessed high drug loading, biocompatibility, stability, and an enhanced retention time. The system was modified with tumor-targeting peptides (RGDyK) to form bioactive cell-specific ligand (RGD-RBC-NCs) that had an advanced tumor accumulation effect on mouse subcutaneous tumor and orthotropic glioma [61]. An approach using folate-based antitumor cell ligands is widely employed for the selective parenteral delivery of therapeutics owing to the overexpression of folate receptors on many cancerous cells. In addition, its cytocompatibility, low immunogenicity, ease of alteration, good tissue penetration, and rapid clearance from cell receptors are salient features that make it an attractive ligand-based approach. Paclitaxel nanocrystals were conjugated with folate-modified PIK-75 (phosphatidylinositol-3-kinase inhibitor) ligand and Pluronic F68 as a stabilizer. The designed system had a higher accumulation and enhanced mean residence time within the target cell (SKOV-3) compared with bare nanocrystals [62]. Atenolol nanocrystals were developed through a bottom-up approach to improve solubility, bioavailability, and permeability. The developed nanocrystals had were tiny and acicular with predicted distinct crystalline peaks. The optimum zeta potential enabled the formulation to be stable and suitable for parenteral administration [63].

1.3 Drug nanocrystals for pulmonary delivery The pulmonary route is suitable for aerodynamic nanocrystal-based drug delivery because it provides an enlarged surface area for drug absorption: the less thickened epithelial layer enables a widespread vasculature or diffusion; the minimum mucociliary clearance or phagocytosis offers efficient drug transport across the lung epithelium. This route minimizes firstpass metabolism; hence, the optimal concentration of drug is attained at the site. Moreover, relatively less enzymatic drug degradation is observed in the alveolar space compared with other tissues and the gastrointestinal tract. These features enable the drug from dosage forms to be well-absorbed with greater therapeutic effect, lowering systemic adverse reactions and related toxicity. Localized direct delivery through inhalation ensures regional drug administration, hindering systemic dilution, and facilitating better accumulation within bronchial or alveolar cells at a low dose [64].

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10. Drug nanocrystals as drug delivery systems

Itraconazole, a BCS Class II drug, was transformed into stabilized nanosuspensions through top-down wet milling. The prepared system was nebulized in rats, which exhibited rapid solubilization and absorption; thus, it efficiently combats cystic fibrosis, a genetic disorder. Patients with allergic bronchopulmonary aspergillosis have colonization of aspergillus infectant and are not effectively treated with oral medicaments. Rundfeldt et al. reported forming an itraconazole nanocrystalline suspension (particle size of 200 nm) stabilized with polysorbate 80 through wet milling. The system was stable at 8 C with no sign of particlee particle aggregation and was easily nebulized through a pressure air nebulizer. Moreover, 10% suspension (45 mg kg
1 dose) was well-tolerated once daily for 7 days, a with maximum lung concentration of 21.4 mg g
1 and a terminal half-life of 25.4 h in rats. The formulation has the potential to mitigate cystic fibrosis accompanied by Aspergillus infection with minimal systemic exposure [65]. Table 10.4 lists drug nanocrystals as carriers for pulmonary delivery. Inhaled dry powder for controlled drug delivery via an encapsulated nanocrystalline approach was reported to eliminate bacterial infection through a pulmonary route. Ciprofloxacin nanocrystals were transformed into liposomal dry powders through freeze-thawing or freeze-drying. The developed spherical nanoparticulate system (particle size of w1 mm) was dispersed with an Osmohaler inhaler at 100 L min
1 for high aerosol efficiency (66e70%). The system exhibited high drug entrapment efficiency (71e79%) and prolonged drug release [73].

1.4 Drug nanocrystals for ocular delivery Drug administration to the ocular site is challenging because of improper dosing, less residence time, poor drug solubility, erratic bioavailability, and the substantial loss of drug owing to tear flow. Nanoengineered drug delivery approaches facilitate the desired therapeutic action by amplifying the surface area, modifying solubility, improving bioavailability, and maintaining stability. Research and development on nanocrystal-based ocular drug delivery have increased because these systems can increase saturation solubility, enhance ophthalmic permeation across the cornea, facilitate controlled release, and prolong retention time with fewer or minimal side effects [74]. Steroidal dexamethasone acetate (0.05%) and antibacterial polymyxin B (0.10%) nanocrystals were developed with cetylpyridinium chloride (0.01%) and benzalkonium chloride (0.01%) through wet bead milling. Improved saturation solubility and prolonged residence time in the ocular region resulted in an efficient system for ophthalmic applications. Furthermore, the presence of a cationic charge facilitated mucoadhesiveness, resulting in enhanced bioavailability. The developed nanoscale preparation (particle size of 200e250 nm) was physicochemically stable (zeta potential of þ20 to þ30) at a wide temperature range (5e40 C) for 6 months. The cationic ophthalmic formulation had no cytotoxic effect on the fibroblast cell culture [75]. Azopt, which was commercialized by Alcon in 1988, contains a reversible carbonic anhydrase inhibitor, brinzolamide (1.0%) as an ophthalmic suspension for the treatment of high intraocular pressure caused by glaucoma. Owing to poor solubility, this drug was unable to provide the desired ocular concentration, and hence had poor absorption and erratic bioavailability. Tuomela and Puranen used nanocrystal technology to transform poorly soluble brinzolamide, which enabled a modified dissolution rate and better efficacy to lower

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165

1. Introduction

TABLE 10.4

Examples of drug nanocrystals used for pulmonary applications.

Dosage form

Method

Research highlights

References

Curcumin spray-dried powder

Wet milling, spray-dried

Effect of milling time on drug [66] particle size, aerodynamic performance, tissue distribution, and pharmacokinetic behavior was studied. Prepared nanocrystals were able to deliver curcumin in lungs after inhalation.

Antiburkholderia agent, C109 poorly soluble FtsZ inhibitor (dry powder inhalation)

[67] Nanocrystals were prepared with D- C109 is an effective drug against a- tocopheryl PEG 1000 succinate as Burkholderia cenopacia, a causative stabilizer and embedded in agent of cystic fibrosis. Developed cyclodextrin derivative rod-shaped C109 nanocrystals diffused cystic fibrosis mucus with no toxicity toward bronchial cells. Conjugation with piperacillin exhibited therapy against pulmonary infections.

Budesonide- hyaluronic acid nanocrystal dry powder

Wet milling and spray-drying

Budesonide nanosuspensions were [68] embedded in hyaluronic acid followed by spray-drying to get fine powder to check rapid clearance from lung tissues. Developed formulation was able to reside in the pulmonary route owing to the suitable size of inhalation and good aerosolization.

Rhodamine-loaded cellulose nanocrystals (CNCss)

Rhodamine-loaded cellulose nanocrystals were isolated from cotton

Interaction of size of cellulose nanocrystals with multicellular epithelial airway barrier revealed that long tunicate CNC prolonged residence in lung tissues owing to lower clearance.

Cinaciguat nanocrystalembedded chitosan microparticles

High-pressure homogenization and spray-drying

[70] Sustained pulmonary delivery system of Cinaciguat-based chitosan particles (3e4 mm) had high payload and promising aerosolization features. The system exhibited swelling and mucoadhesion owing to chitosan, providing sustained release throughout bronchial airway.

Baicalein nanocrystals

[71] Antisolvent crystallization and high- Prepared baicalein is a flavone pressure homogenization inhibitor of Staphylococcus aureus biofilm. Prepared nanocrystals displayed a high dissolution velocity and significant adsorption through bronchial mucosa.

[69]

(Continued)

V. Drug delivery

166 TABLE 10.4

10. Drug nanocrystals as drug delivery systems

Examples of drug nanocrystals used for pulmonary applications.dcont’d

Dosage form

Method

Research highlights

References

ZnO-doped TiO2 nanocrystals

Chemical method

The study aimed to reduce the cytotoxicity effect of ZnO-doped TiO2 particles in pulmonary A549 cells. Developed nanocrystals had antibacterial activity against a wide range of pathogens cultured in pulmonary pathway.

[72]

the intraocular pressure in glaucoma and cure other ocular disorders. The effect of various stabilizers (i.e., HPMC, poloxamer F127 and F68, and polysorbate 80) was monitored for particle size, morphology, polydispersity, and dissolution in pH 4.5 and 7.4. The prepared nanocrystals were 100% solubilized at pH 7.4 within 1 min. The cytotoxic study carried out in human corneal cells exhibited a significant reduction in intraocular pressure compared with the marketed preparation [76]. Innovative lipid-based drug nanocrystals are being investigated to overcome barriers related to the physiology and anatomy of the eye. An in vivo study of this system revealed an extended therapeutic effect, better absorption, amplified bioavailability, and pronounced permeation followed by sustained release compared with conventional ophthalmic dosages [77]. Table 10.5 lists drug nanocrystals designed for ophthalmic drug delivery. TABLE 10.5

Drug nanocrystals used for ocular administration.

Therapeutics

Research objective

Outcomes

References

Pilocarpine HCl Influence of cellulose nanocrystals (CNCs) nanocrystalline on triblock poloxamer copolymer (PM) gel and in vitro release of pilocarpine from nanocomposites was studied.

The optimal concentrations of CNCs [78] (16.6% w/v) and PM (18 % w/v) were adjusted to prepare in situ pilocarpine gel. A sustained effect was obtained revealing the Fickian diffusion mechanism.

Lutein nanocrystals

The bottom-up approach was used to improve the ocular distribution of lutein.

Developed nanocrystals showed increased [79] dispersion and dissolution behavior. The ocular accumulation of lutein nanocrystals were 3.4-folds higher compared with crystalline lutein.

Atenolol nanocrystals

Permeability of BCS Class III drug atenolol was modified through the nanocrystal approach.

Prepared nanocrystals were positively [80] charged and had potential for ophthalmic drug delivery.

Ibuprofen nanocrystals

A two-by-two factorial design was applied to optimize the surfactant concentration (Tween 80, Span 80, and PVP K30) to develop stable nanocrystals.

Formulations containing 0.2% Tween 80: [81] 1.2% PVP K30%, and 0.2% Tween 80: 0.2% Span 80 were stable and suitable for ocular drug delivery.

Hydrocortisone Hydrophobic hydrocortisone was nanosuspension transformed into nanocrystals through microfluidic precipitation to modify its solubility.

Nanosized (300-nm) stable nanocrystals were developed that exhibited sustained drug release for 9 h in albino rabbit. Improved ocular bioavailability was observed.

V. Drug delivery

[82]

1. Introduction

167

1.5 Targeted drug delivery via nanocrystals Poor solubility, hindered bioavailability, and nonspecific distribution in the body lead to undesirable effects, restricting clinical applications such drugs. Various nanocarriers such as polymeric nanoparticles, liposomes, micelles, and niosomes are extensively used for drug targeting, but the drug nanocrystal strategy is cost-effective, highly payloaded, stable, and feasible for scaling up with both top-down and bottom-up methods. Flexible size dimensions (a few hundred nanometers), physical stability, and the absence of a chemical carrier enable nanocrystals to deliver the drug at low concentrations [83]. Because they are composed of a pure drug (w80% w/w), nanocrystals are well-suited for cell-level drug delivery, because toxic effects caused by encapsulation, leaks, bursting, and other physical instabilities associated with nanocarriers are also eliminated [84]. After intravenous administration, drug nanocrystals are preferentially transported into the liver, spleen, and lung through the mononuclear phagocytic system (Fig. 10.5). Therefore, they are preferred dosage forms for targeting cells present in these organ systems [85]. Efficient uptake by mononuclear phagocytic system and enhanced residence time facilitate curative and successful therapy. Free drug (particle size of 200e500 nm) from nanocrystals is also taken up and internalized by active transport through clathrin and caveolae-mediated endocytosis [86]. Poorly soluble ( (nanocuboid) with respect to the density of Fe3þ-exposed planes. Hematite nanocrystals are environmentally friendly catalysts because they could be regenerated using magnetic separation and recycled efficiently up to six cycles in the photocatalytic degradation of methyl orange [59] (Fig. 15.16).

FIGURE 15.16 HRTEM images of differently shaped hematite nanocrystals nanorods, nanocuboids, bitruncated octahedrons, and bitruncated dodecahedrons. Reprinted (adapted) with permission from A.K. Patra, S.K. Kundu, A. Bhaumik, D. Kim, Morphology evolution of single-crystalline hematite nanocrystals: magnetically recoverable, Nanoscale. (2015). Copyright 2021 Royal Society of Chemistry. VI. Catalysis

5. Nanocrystals in photocatalysis

305

5.2 Perovskite nanocrystals in photocatalysis Green photocatalysts such as perovskites are widely applied for the degradation of organic dyes. Barium zirconate perovskite doped with bismuth nanocrystals is an effective green photocatalyst for the degradation of methylene blue in UV and sunlight. Cubic BaZrO3 with monoclinic-phase ZrO2 was obtained by hydrothermal synthesis and bismuth was doped into BaZrO3, which increased the monoclinic phase segregation of ZrO2. Also, the barium zirconate (BZO) crystalline size increased from 72 to 144 nm and the ZrO2 crystalline size decreased from 32 to 26 nm owing to Bi doping. As the Bi concentration increased, more defect bands were generated in BZO and UV-vis adsorption shifted toward red. Highly Bi nanocrystals doped were a UV-vis light photocatalyst because the UV-vis absorption edges red-shifted in the visible region and narrow bandgaps. BaZr1-xBixO3 is a green photocatalyst for the degradation of methylene blue, where x ¼ 1% BaZr1-xBixO3 degrades 34% of methylene blue (MB) under UV light and x ¼ 10% degrades 87% of MB under solar radiation [60].

5.3 Copper oxide nanocrystals in photocatalysis Copper oxide nanocrystals are an efficient photocatalyst. Truncated octahedral Cu2O nanocrystals with eight (111) faces and six (100) faces is 14-faced. Ordered nanocrystals were supported on an Si substrate. Comparison of the photocatalytic efficacy of the ordered and disordered Cu2O nanocrystals for the degradation of methylene blue under visible light resulted in 36% and 88%, respectively. Ordered Cu2O nanocrystals prominently degrade MB owing to the ordered array of (111) planes that reflect visible light, actively leading to better degradation than disordered nanocrystals. These Cu2O nanocrystals have remarkable recyclability up to nine cycles with no significant loss in reactivity as a photocatalyst [61] (Fig. 15.17). Cu2O@Cu7S4 core-shell micro/nanocrystals were synthesized by a sacrificial Cu2O template

FIGURE 15.17 Schematic illustration of photocatalytic activity of truncated octahedral Cu2O under visible light. Reprinted (adapted) with permission from X. Wei, J. Pan, J. Mei, Y. Zheng, C. Cui, C. Li, Photonics and nanostructures e fundamentals and applications the orderly nano array of truncated octahedra Cu2O nanocrystals with the enhancement of visible light photocatalytic activity, Photon. Nanostruct. Fundam. Appl. 30 (2018) 20e24. Copyright 2021 Elsevier.

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15. Sustainable catalysis of nanocrystals: A green technology

based on the Kirkendall effect, and the core-shell was achieved by varying the concentration of Na2S⸱9H2O. Cuboctahedron-shaped nanocrystals were observed from field emission scanning electron microscope (FESEM) images with six square {100} and eight triangle {111} facets. These nanocrystals possess a special arrangement of Cu atoms and O atoms on the crystalline plane, which increased the adsorption ability and photocatalytic degradation of MB under visible light. Cu2O@Cu7S4 core-shell micro/nanocrystals have higher degradation ability than the pure Cu2O phase. The special structure of Cu2O@Cu7S4 core-shell micro/nanocrystals enables Cu atoms on the surface with negatively charged SO3 on MB for improved photocatalytic degradation under visible light [62].

5.4 Cadmium nanocrystals in photocatalysis CdS nanocrystals of different shapes and structures have different photocatalytic efficiency in the degradation of organic dye under visible light at room temperature. CdS nanocrystals of different morphologies and phases, such as hexagonal nanospheres (CdS-1), hierarchical caterpillar-like fungus nanorods (CdS-2), and hierarchical cubic microspheres (CdS-3), were prepared by a one-pot microwave-assisted chemical process. The bandgap energy calculated for these three CdS nanocrystals revealed a red shift induced as the result of internal structural defects (Fig. 15.18). These results revealed that CdS nanocrystals can activate the photocatalytic degradation of organic dyes such as rhodamine B and methylene blue under visible light. Among the three nanocrystalline CdS, the cubic sphalerite CdS nanocrystal showed better photocatalytic degradation of MB and rhodamine B, which may be because of the lower bandgap energy, weaker combination of electrons and holes, and hierarchical porous structure for the adsorption of substrate. Cubic CdS nanocrystals had superior photocatalytic efficacy and stability for the degradation of organic dyes under visible light and better recyclability up to four times with retained reactivity compared with nanosphere and nanorod CdS nanocrystals [63]. FIGURE 15.18 XRD pattern of different crystalline structures of CdS. Reprinted (adapted) with permission from C. Deng, X. Tian, Facile microwave-assisted aqueous synthesis of CdS nanocrystals with their photocatalytic activities under visible lighting, 48 (2013) 4344e4350. Copyright 2021 Elsevier.

VI. Catalysis

5. Nanocrystals in photocatalysis

307

5.5 Tin oxide nanocrystals in photocatalysis Fe-doped SnO2 nanocrystals have effective photocatalytic degradation of rhodamine B under visible light radiation. The Brunauer-Emmer-Teller (BET) surface area analysis after Fe doping increased to 10% compared with undoped SnO2 nanocrystals, which may be effectively used in gas detection, photocatalysis, and so forth. Mössbauer spectroscopy proves distortion in SnO2 due to Fe doping increasing defects in the crystal structure, which produces an oxygen vacancy due to charge balance requirement. Photocatalytic properties under visible light for Fe-doped SnO2 nanocrystals were improved owing to subband gap transition energy. Under visible light, Fe-doped SnO2 nanocrystals charge separation between electron and hole improved the photocatalytic degradation of rhodamine B. In addition, a lower recombination rate and increased BET surface area subsequently increased photocatalytic degradation under visible light. Upon increasing the doping content of Fe on SnO2, catalytic activity decreased because of the increase in disorderliness and the reduced mobility of photogenerated charge carriers to reach the surface [64].

5.6 Magnetic nanocrystals in photocatalysis MnFe2O4 anchored on CNC has 3.6 times the increased surface area compared with bare MnFe2O4, which will improve the catalytic ability. As an important factor for photocatalysis, the bandgap energy for the MnFe2O4/CNC nanocomposite is reduced compared with bare MnFe2O4 nanoparticles, which improves photocatalytic efficiency. Also, MnFe2O4/CNC nanocomposites along with H2O2 remarkably enhance the degradation of methylene blue. This can be attributed to the easier approach of hydroxyl radicals with MB. MnFe2O4/CNC can be recovered and reused by magnetic separation for five cycles for the photocatalytic degradation of methylene blue with no significant loss in catalytic ability and activity [65].

5.7 Titanium oxide nanocrystals in photocatalysis ZnO and TiO2 nanocrystals are efficient photocatalysts for the degradation of chlorpyrifos under sunlight. Of the two, TiO2 nanocrystals are more prominent than ZnO nanocrystal because TiO2 nanocrystals are smaller in size with a larger surface area enhancing adsorption capacity in an acidic environment [66].

5.8 Conclusions The photocatalysis of nanocrystals has special consideration in the field of the degradation of dye and other contaminants present in textile and leather industrial effluents. These nanocrystals were effective and efficient in photocatalysis owing to their perfect crystalline structure, shape, and size. Apart from the activity of nanocrystals in photocatalysis, their recoverability and reusability have special attention in catalysis. Nanocrystals as such or supported nanocrystals provide excellent durability, low toxicity, and high crystallinity for use as photocatalysts. Supported nanocrystals provide easy separation of the catalyst material through filtration, centrifugation, and magnetic separation. Such a novel nanocrystal catalyst design may bring new insight to green recyclable photocatalysts in the environmental protection field.

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15. Sustainable catalysis of nanocrystals: A green technology

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S E C T I O N V I I

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Application of nanocrystals as antimicrobials N. Vigneshwaran, A. Arputharaj, N.M. Ashtaputre and Charlene D’ Souza ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India

1. Introduction Microbial contamination and their attack on various surfaces pose major problems in medical sector as well as in various industries such as textiles, pulp and paper, foods and beverages, chemicals and biochemicals, water and effluent treatment, electronics and telecommunication, and pharmaceuticals. Some types of microbial attack can be controlled by adding microbiocides, whereas others warrant the complete replacement of machine parts and systems. Physical means of controlling microbes are traditional methods that start with maintaining hygienic conditions in the working environment followed by heat treatment, high pressure, desiccation, drying, and filtration. Advanced physical techniques include the use of radiation such as ultraviolet (UV) rays, X-rays, electron beams, and gamma rays. Although advanced physical techniques are costly, they are highly effective and efficient. Chemical means include the use of antibiotics, alcohols, oxygen, ozone, halogens, phenolics, heavy metals and their compounds, aldehydes, detergents, and quaternary ammonium compounds. These chemicals have become popular because of their ease of handling in various places and conditions and their versatile means of packaging and transport. Chemical means of sanitization have also become popularity for widespread use during the COVID-19 pandemic. Plant metabolites including tannins, quinines, alkaloids, polypeptides, flavones, flavonoids, coumarin, terpenoids, and essential oils are being explored as antimicrobials to circumvent the problems of developing antibiotic resistance. To some extent, the use of biological materials such as enzymes, bacteriophages, and antimicrobial peptides are being tried as antimicrobials. Despite these developments in the widespread use of various antimicrobial agents in different sectors, there are always lacunae in existing methods in terms of their cost-effectiveness, efficiency, environmental safety, handling issues, and disposal hazards.

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FIGURE 16.1

Different categories of nanomaterials used for antimicrobial action.

Metals Metal oxides

Hybrids

Carbon

Antimicrobial nanocrystals

Dendrimers

Polymers

Micelles Liposomes

With advances in the field of nanotechnology, a category of antimicrobials called nanocrystals is being widely exploited in various industries. Nanocrystals are produced from metals, metal oxides, polymers, carbon, and their hybrid forms. To improve the efficiency of these nanomaterials, micelles, liposomes, and dendrimers are used. Apart from basic material properties, others such as the particle size, surface energy, surface charge, shape, photocatalysis, release of free radicals, and other size-dependent attributes contribute to enhance antimicrobial properties. Different categories of nanomaterials used as antimicrobial agents are shown in Fig. 16.1.

2. Nanomaterials and their mode of action Nanomaterials became important after the invention of atomic force microscopy in 1985 and carbon nanotubes (CNTs) in 1991. These were followed by various inventions in the field of nanotechnology for diversified applications. Nanomaterials were initially applied in textiles for commercial application followed by pharmaceuticals and electronics. Nanomaterials are demonstrated for application in the field of agriculture as well as food and beverages. Despite their excellent potential for application, bottlenecks faced in synthesizing nanomaterials limit their applications. Two major approaches to synthesizing nanomaterials are top-down and bottom-up. In the top-down approach, bulk or micromaterials are reduced in size by providing energy to production nanoparticles. Techniques such as ball milling, homogenization, microfluidization, etching, and grinding

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are commercial top-down approaches. In the bottom-up approach, atoms or molecules are assembled or aggregated to form nanomaterials, with the subsequent release of energy. Techniques such as oxidation/reduction, sol-gel, sonochemical, microemulsion, coprecipitation, pyrolysis, solvothermal, and electrolysis are conventional bottom-up approaches. In addition, green chemistry and microbial and biological processes are being explored for the environmentally friendly production of nanomaterials. In the case of the topdown approach, productivity is high whereas size distribution is wide and is a lot of contamination. In case of bottom-up approach, the productivity is low while the sizedistribution is very narrow. Hence, depending on the applications, the type of production method has to be chosen for the use of nanomaterials. Common examples of various nanomaterials used for antimicrobial properties are listed in Fig. 16.2. With regard to the mode of action, some nanomaterials act similarly to that of conventional antimicrobials and others act in an entirely different way. Nanomaterials such as silver and zinc release metal ions, leading to heavy metal toxicity in microorganisms. Heavy metal ions bind irreversibly to proteins and enzymes, resulting in denaturation and deactivation. Some materials having inherent antimicrobial properties, such as chitosan, showing enhanced activity in their nano-form primarily owing to a large surface area. Because of the nano-size, these particles can easily enter the cell membrane of microbes and result in DNA damage. Photocatalytic nanoparticles such as nano-titania produce radicals that can cause severe damage to microbes. Hydrophobic nanomaterials can be coated onto various surfaces to avoid biofilm formation. Electrostatic interaction is a prominent mode of antimicrobial action in nano-chitosan. Positively charged chitosan molecules interact with negatively charged lipopolysaccharides of gram-negative bacteria and teichoic acids of gram-positive bacteria, resulting in cell wall disruption. Fig. 16.3 shows various modes of antimicrobial actions of various nanomaterials.

Metals

Silver

Copper

Gold

Metal oxides

Zinc oxide

Copper oxide

Titanium oxide

Polymers

Chitosan

Peptides

Lignin

Carbon

CNTs

Graphene

fullerene

Ceramics

Barium Zirconate Titanate

Doped hydroxy apatite

Doped nanoclay

FIGURE 16.2 Common examples of antimicrobial nanomaterials. CNTs, carbon nanotubes.

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FIGURE 16.3 Modes of antimicrobial action of various nanomaterials.

Oxidative stress Inhibition of cell wall synthesis

Resist biofilm formation

Interruption of electron transport

Mode of action of nanomaterials

Penetration of cell membrane

Enzyme inactivation

DNA damage Protein denaturation

3. Nano-silver Among the noble metals, silver enjoys the privilege of being the most well-studied noble metal as far as nanotechnology is concerned. The main reasons are its abundance and its physical properties such as malleability, ductility, good thermal and electrical conductivity, high corrosion resistance, scratch resistance, and antimicrobial property. Since the advent of nanotechnology, the synthesis of silver nanoparticles has been studied extensively, leading to myriad shapes with versatile properties and a plethora of applications depending on the shape and size of the nanoparticles. Silver nanocrystals exhibit a high level of antibacterial properties. Silver nanoparticles in the size range of 10e100 nm display a broad spectrum of antimicrobial activity with 100% cidal effect against most common pathogens such as bacteria, fungi, and viruses even when used at a low concentration. The antibacterial effect of silver nanocrystals can be attributed to four mechanisms. Ionic silver has an affinity for the sulfur moiety present in the cell wall and cytoplasmic membrane proteins. Therefore, silver nanoparticles become lodged in the cell, interfering with different receptors and inhibiting respiration. Nanoparticles enter the cell, deactivate the enzymes, and disrupt nucleic acid replication, forming insoluble compounds with the nucleotides, proteins, and the amino acid histidine and making them unavailable as intracellular building blocks, leading to death of the cell [1]. Because of this chemical bonding mechanism, microbes that usually develop resistance to antibiotics upon frequent exposure to antibiotics fail to do so in the case of silver nanoparticles, which is a major advantage. There some applications of silver nanocrystals in the medical sector: (1) Wound dressings impregnated with silver nanoparticles, especially biosynthesized ones, are beneficial for two reasons: their antibacterial activity and their biocompatibility. Biosynthesized nanoparticles are invariably biocompatible; thus, they prevent

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aerial pathogens from infecting the wounded tissue with no allergic response (e.g., electrospun polycaprolactone wound dressings with biosynthesized silver nanoparticles incorporated into them are excellent because they release silver ions over a certain period, which helps prevent the proliferation of pathogens) [2]. However, one aspect that needs to be addressed is cytotoxicity toward human tissue cells upon prolonged exposure to these crystals, because they may be absorbed into the system and cause toxicity or lead to a condition called argyria, which causes skin and eye discoloration. In the case of chronic or exudating wounds, hydrogels made of hydrophilic polymers are beneficial because they keep the wound dry. For such hydrogels, when loaded with silver nanoparticles (AgNPs), the benefit is doubled owing to the antibacterial and antifungal properties that expedite wound healing. (2) In dentistry, traditionally, silver and gold were the main noble metals of choice for making dental amalgams for restoring teeth. These were followed by the revolutionary use of synthetic polymeric resins that imparted strength to teeth at an economical cost. The multiple benefits of silver nanoparticles are now incorporated into making oral care formulations, dental implants, adhesives, composites, and so forth, preventing biofilm formation and dental caries, which is a major oral disease globally, especially in children. Silver diamine fluoride (SDF) used in young children as a therapeutic agent has with dual purpose. It arrests caries because of the antibacterial effect of silver, and teeth are strengthened owing to the fluoride component [3]. However, a disadvantage of using SDF is that silver compounds become precipitated in dental tissues, imparting a permanent black color to lesions, and temporarily to the skin and gingiva, which is unsightly. This can be overcome by using a 0.1% by weight nano-silver powder and fluoride varnish, the effect of which lasts for at least 3 months [4]. (3) The use of central venous catheters for long periods may result in bacterial infections that may prove fatal to patients. Silver nanoparticle-impregnated catheters have proven to be a boon because of the strong antibacterial activity of nanocrystals [5]. (4) In orthopedics, biomaterials used as bone cement loaded with AgNPs were beneficial because of the antibacterial property of AgNP against all major pathogens including methicillin-resistant Staphylococcus aureus (MRSA) [5]. In agriculture, the rampant use of pesticides has many disadvantages. It results in resistant strains of pathogens and poses a threat to the environment by the absorption of pesticides in runoff waters, causing a grave loss of flora and fauna and causing harmful residual effects to higher animals and humans who consume these agricultural products treated with chemical pesticides. The use of silver nanoparticles is helpful in agriculture owing to its strong antimicrobial activity with the advantage that silver is a biostimulant. Nano-based formulations remain stable and are cost-effective, hence, they can be used safely at small concentrations. Earlier research [6] demonstrated the antifungal effect of nano-silver liquid against white rot fungus, Sclerotium cepivorum, in green onions. In textiles, antimicrobial protection controls the spread of disease and danger of infection after injuries, controls the development of odors from perspiration, and controls the deterioration of textiles by mildew or rot-producing microbes. Fabrics, especially those made from natural fibers such cotton and wool, are susceptible to microbial attack because the major component of cotton is cellulose and that of wool is protein, which are excellent sources of

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nutrients and energy. Cellulose can easily be degraded by cellulase enzymes produced by many microorganisms. Thus, fabrics need to be treated to protect them from microbial attack. This treatment of fabrics is termed finishing; it may be biostatic (i.e., only controls the growth and spread of microbes or biocidal, killing microbes). Antibacterial agents used industrially include quaternary ammonium salts, metal solutions, and antibiotics. However, the rise in resistant pathogenic strains is a major problem because microbes tend to form biofilms in which microbes undergo constant mutation. The use of silver nanocrystals in the textile industry has increased owing to their excellent antimicrobial activity. Moreover, they are safe because they have no adverse effects on the normal flora of human skin. Silver nanocrystals can be applied to fabrics by soaking them in nanoparticle solutions in the presence of a binder and subjecting them to a pad-dry-cure process [7]. The other method is the in situ synthesis of silver nanoparticles in a textile matrix. In the former method, a silver salt dissolved in an appropriate solvent is reduced using a reducing agent such as sodium borohydride, which helps in the rapid formation of silver nuclei, further developing into nanocrystals of a uniform particle size. In in situ AgNP synthesis, that fibers of fabrics soaked in water have a negative surface charge is used to attract and bind positively charged silver ions from the solution of a silver salt. These Agþ ions bound on the surface are reduced by adding a reducing agent such as NaBH4, trisodium citrate, ascorbic acid, starch, and glucose [8]. This method ensures the even distribution of AgNP on the surface of the fabrics. A major advantage of in situ synthesis is that because the adherence of AgNP occurs on the surface of the fabric, end groups of cellulose molecules help to stabilize the nanocrystals, eliminating the need to add a stabilizer. Electrospinning is another development in nanotechnology. In this technique, fibers can be spun using a solution of a polymer that is ejected through a spinneret under a high-voltage electric field, which solidifies to form a filament. These fibers can be made to carry AgNP. There are two methods: nanofibers can be spun along with silver salt solution or they can first be spun and then treated for the in situ synthesis of AgNP. Shi et al. [9] described the one-step synthesis of AgNP-filled nylon 66 nanofibers using formic acid (solvent) as a reducing agent and the polymer as a stabilizer. The nanofibers provided the steady release of silver ions over a long period with almost 100% antibacterial activity. Since that research, electrospinning nanotechnology has come a long way, with the focus shifting to the possible use of natural polymers and composite fibers of natural and synthetic polymers with embedded AgNP using electrospinning [10]. In water purification, filter membranes have an important role. Depending on their porosity, they can be applied to get different grades of water. As far as potable water is concerned, membranes with dual action (filtering contaminants and killing microorganisms) are preferred. The best solution to achieve this is to prepare functionalized filter membranes with high porosity and small fiber diameters yet high tensile strength. An additional property of high antibacterial activity could be imparted by embedding AgNP in the matrix. This has the added advantage of slow release with a prolonged effect. Pan et al. [11] synthesized 10-nm monodisperse AgNPs in situ in a polyacrylonitrile nanofiber mat with outstanding hydrophilicity, resulting in high water fluxes in forward and reverse osmosis and good antibacterial activity, preventing biofouling. In the food industry, because they are highly nutritious, foods are susceptible to microbial attack if they are not covered and stored under proper conditions. Plastic had been the

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preferred material to store foods until its drawbacks came to light. Plastic is a lightweight, synthetic, and economical packaging material obtained as a by-product of the petroleum industry. It is nonbiodegradable and thus is discouraged in daily use. An alternative to plastics is bioplastic made from biopolymers such as gelatin and chitosan, which are biodegradable. Films made from these polymers have barrier properties against water-vapor. However, their mechanical and antimicrobial properties are not up to required standards. To address these issues, research is being carried out on additives such as starch, nanocellulose, and other fillers to increase the mechanical strength and use of biosynthesized nano-silver to impart good antibacterial activity. To protect buildings, vehicles, and machines from damage and rust, their surfaces are painted. However, paints are also susceptible to microbial and fungal attack because they may contain organic components. These organic components make paint a nourishing medium to organisms, which produce many enzymes that may destroy cellulose-based thickeners, affecting the viscosity and causing discoloration. To prevent the contamination and discoloration of painted surfaces, the addition of biocides to paint is necessary. Since the advent of nanotechnology and knowledge about the antimicrobial property of silver nanoparticles was popularized, trials were run to add AgNP to paints to make them resistant to microbial attack. Bellotti et al. [12] synthesized AgNPs using gallic acid at an alkaline pH using NH4OH. When added to paints, this imparted good fungal resistance. Moreover, the gloss of paints remained unchanged despite the addition of silver nanoparticles.

4. Nano-copper Since ancient times, noble metals and their alloys have been used in some form for various medicinal applications throughout Greece, Egypt, Persia, Rome, and India. Some of these were documented in ancient papyrus writings as early as 2400 BCE. Copper, silver, and gold vessels were used for important and auspicious duties such as religious worship utensils and also by royalty. The salts of these noble metals had antibacterial and antifungal applications. The indiscriminate use of antibiotics in antibacterial therapy has yielded a large number of pathogens resistant to regularly used antibiotics. MRSA is a commonly cited example. Because of the development of multiple drug resistance in pathogens, modern researchers began retracing the footsteps of ancestral therapists and investigated the chemistry of ancient medicine. A common form of antimicrobial therapy was the use of colloidal solutions. Many used combinations of plant extracts and ferments with noble metal salts to obtain these colloids, some of which are still popular as wellness agents. Mixtures of copper salts/oxides with honey, vinegar, wine, rose oil, and so on were effective against a wide variety of pathogens, from ulcers, bacterial conjunctivitis, and boils to lung diseases such as tuberculosis. These colloids are micro- and nanosized structures formed possibly by the reduction of ionic copper to zero-valent copper nanocrystals by organic reducing compounds found in many of the ferments and plant extracts. Although actual work in the field of nanotechnology began after 1950, its principles were already being applied in the field of traditional medicine all over the world.

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The advent of metal nanoparticles opened a Pandora’s box of antimicrobial therapy. The preparation of these nanocrystals may involve physical or chemical methods involving laser ablation, thermal decomposition, chemical reduction, and polyol synthesis; one of the most economical and efficient is the chemical reduction method. Preparation of metal nanocrystals by chemical reduction primarily involves a metal precursor salt or even its oxide, a reducing agent, and a stabilizer or capping agent. Copper salts (acetate, nitrate, sulfate, and chloride) with different reducing agents such as sodium borohydride and ascorbic acid are used. Polymeric and organic substances such as starch, polyphenols, and chitosan are used as stabilizers. Other factors such as the pH, mixing or stirring speed, reaction time, temperature, and molar ratio of the precursor to reducing agent and capping agent as well as combinations of different precursors with reducing agents may be used to create crystals of various sizes and morphologies. To reduce the environmental pollution load in synthesizing these nanoparticles, researchers are investigating green methods. Reducing agents commonly used are inherent peptides, amino acids, pigments, and quinones found in aqueous plant extracts. Green synthesis yields residues of comparatively lower toxicity, better biocompatibility and biodegradability and ensures a process that is economically viable and often renewable in terms of resource consumption. The antimicrobial properties of nanoparticles depend on their shape, size (the smaller the size, the higher the mortality), concentration (which is directly proportional to mortality), dosage, surface properties, surrounding media pH, exposure time, type of reactive oxygen species (ROS) generated, sensitivity of the microorganism, and age of the target species. Raffi et al. [13] demonstrated that in Escherichia coli, after exposure to copper nanoparticles, the cell wall developed cavities. Copper, a micronutrient required for cellular activities, showed inhibition at higher concentrations. They are also believed to bind to sulfur- and phosphorus-containing compounds such as proteins and DNA. In addition, they produce hydrogen peroxide, which damages the cytoplasmic membrane. Slavin et al. [14] showed that the E. coli cell wall has a higher electrostatic negative charge and is therefore more rigid than gram-positive S. aureus. This could be the reason for the higher susceptibility of S. aureus to negatively charged metal nanocrystals and ROS. They also described they periplasmic localization of nanomaterials. Transition metal nanocrystals bind to thiol (eSH) groups. Both ionic and nano forms damage the three-dimensional structure of proteins by breaking SeS bonds and destabilizing the tertiary structure of enzyme proteins, interfering with functional operations such as respiratory electron transport chains, which are vital to the survival of the microorganism. Interference in oxygen transport into the cell (for aerobes) inhibits the expression of proteins associated with adenosine triphosphate production. Smaller nanomaterials are directly proportional to the increased surface area available for interaction, leading to an increased amount of ROS, which were described by various authors as the primary cause of antibacterial activity. Gold nanoparticles bind at different ratios to different proteins, depending on their structure. Prabhu et al. [15] demonstrated the higher antibacterial effect of green synthesized copper nanoparticles using mangosteen leaf extract on S. aureus compared with E. coli. They defended this observation by explaining that the presence of teichoic acids and mucopeptides and the capacity to produce antioxidant enzymes results in stronger oxidant resistance. Moreover, S. aureus has a lower negative charge compared with E. coli, allowing negatively

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charged free radicals such as superoxide (eO2) and hydroxyl radicals (eOH) generated by copper nanoparticles to penetrate the cell wall and membrane pores and cause cytoplasmic disruption, ultimately leading to cell death. Depending on the size of the copper nanocrystals, their mechanism of action could vary in a manner similar to other metal nanocrystals. Xia et al. [16] described through atomic force microscope (AFM) imagery how tannic acidcapped copper nanoclusters selectively inhibit the growth of gram-positive bacteria by disrupting their cell membrane after 10 min exposure to a concentration of 30 ppm. Slavin et al. [14] reported that bacteria isolated from heavy metal contaminated environments had a higher tolerance to the antibacterial effects of heavy metal nanomaterials, whereas others regulated cellular activities similar to defense responses such as increased extracellular polysaccharide production that entrapped the nanoparticles and decreased their toxicity. These observations may indicate that bacteria could develop resistance to nanomaterial toxicity after prolonged or indiscriminate exposure.

5. Metal oxide nanoparticles Metal oxides typically contain an anion of oxygen in the oxidation state of 2 and have an intrinsic charge separation capacity. Most of the metals have an oxide form such as magnesium oxide (MgO), ferrous oxide (FeO), or copper oxide (CuO). By modifying the composition and structure of metal oxides, their physical, magnetic, optical, and chemical properties can be modified. Because of this, a lot of interest was created among chemists about this group of substances. The industrial exploitation of metal oxides includes different purposes such as ceramics and catalysis. However, after evolution of the concept of nanotechnology, there was a paradigm shift in the understanding and application of metal oxides. Materials exhibit entirely different physiochemical properties in the form of nanoparticles of metal oxides (MONPs) and are very different from their bulk counterparts in several aspects such as their surface and thermal, electrical, catalytic, and optical properties. Engineered MONPs are among the most well-researched and highly industrially manufactured nanomaterials because of their unique properties. Besides these industrial applications, some MONPs are useful antimicrobials owing to their good bacteriostatic or bactericide properties. MONPs of zinc (ZnO), magnesium (MgO), titanium (TiO2), and copper (CuO) have antimicrobial properties. Among three main classes of antimicrobials (i.e., disinfectants, antiseptics, and antibiotics), MONPs are classed as antiseptics. MONPs are used in the pharmaceutical, cosmetic, food, and textile industries as antimicrobial agents. If we consider the commercial availability of the powered form of nanomaterials, the contribution of metal oxides is the highest. Researchers have adopted various methods for producing MONPs using different precursors and reaction conditions. There are three types of protocols: chemical, biological, and physical methods. Fig. 16.4 shows the different methods used to synthesize MONPs. The variety of wet chemical and physicochemical methods used to fabricate MONPs can modify the characteristics and control the properties of the resultant product. The functionality of MONPs is influenced by their shape, size, chemical composition, crystalline structure, surface charge, morphology interactions of the phases, and so forth. Many methods are reported, but only a few methods are used for the industrial manufacture of MONPs.

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FIGURE 16.4 Classification of synthesis methods of metal oxide nanoparticles. CVD, chemical vapour deposition.

Metal oxide nanoparticles Physical

Ball milling

Biological

Chemical

Gas phase

Plants mediated

Liquid phase

CVD

Pyrolysis

Hydrothermal

Laser ablation

Gas condensation

Solvothermal

Microbes assisted

Sol-gel

Precipitation Microwave method

The oldest and closest reference for ZnO was found in the Charak Samhita, an ancient Indian medical text that dates to 500 BCE. This text describes a healing salve called pushpanjan, which was used to treat open wounds. ZnO, also known as Lu-Gan stone in China, has been used as a medical treatment for many centuries. Interest has arisen in this material because of advances in growth technologies to produce different nanoforms of this metal oxide. ZnO nanoparticles (NPs) have a wide range of antimicrobial activity against various microorganisms, depending on the chosen concentration and particle size. The study of antibacterial activity of ZnO has been reported for several microbes including Neisseria, Gonorrhoea, Proteus mirabilis, Klebsiella, Streptococcus mutans, Vibrio cholerae, E. coli, S. aureus, Serratia marcescens, and Citrobacter freundii and on fungi such as Aspergillus flavus, Aspergillus nidulans, Aspergillus niger, and Candida albicans using Trichoderma harzianum and Rhizopus stolonifera. Three important factors considered to be responsible for bacterial death owing to ZnO NPs are (1) cell function destruction via particle invasion, (2) ROS attack, and (3) the surface affinity of nanoparticles causing membrane damage. Research studies indicated that ROS formation is the main mechanism responsible for ZnO-NP antibacterial activity. ZnO differs from other metal and metal oxide NPs in terms of bactericidal properties owing to the requirement for comparatively higher concentrations to inhibit the growth of pathogenic microorganisms, because it is an essential micronutrient element for prokaryotic organisms [17]. However, the inhibition of many bacteria by Zn2þ ions at a higher concentration illustrates that the concentration of ZnO is an important factor for killing pathogenic bacteria. Gram-positive bacteria are more susceptible to inhibition by ZnO particles compared with gram-negative bacteria, and thus the growth inhibition of gram-negative bacteria occurs at higher ZnO concentrations [18]. ZnO NPs with positive surface potential upon interaction with negative surface potential of the bacterial membrane enhances the production of ROS and exerts mechanical stress on the membrane, resulting in membrane depolarization [19].

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Copper oxide (CuO)/cupric oxide/copper (II) oxide is a black stable metal oxide of copper with a monoclinic structure. Copper oxide is mostly appreciated for its gas sensing and as an electrode in batteries. However, CuO NPs have gained widespread attention owing to their pharmaceutical and therapeutic applications. CuO NPs exhibit bactericidal properties for a broad spectrum of bacterial species, including some multidrug-resistant bacteria such as the superbug MRSA. Moreover, CuO NPs are more effective against gram-negative species such as E. coli and Klebsiella pneumonia than against gram-positive bacterium. This property differs from that in ZnO NPs [20]. Not only on bacteria, CuO NPs are effective against viruses such as influenza virus, poliovirus, human immunodeficiency virus, and bronchitis virus. The green approach to synthesizing CuO NPs using fungi, bacteria yeast, and plant extracts has become the major focus of researchers because of its application requirements [21]. CuO NPs synthesized by the green route have great wound-healing properties compared with commercial wound ointments. Magnesium oxide is a white hygroscopic solid mineral historically known as magnesia alba. It has been used as a purgative medicine. In the presence of water, it undergoes a quick reaction and forms magnesium hydroxide, in which it differs from other antimicrobial metal oxides. Magnesium is an important essential nutrient for the human body, and MgO is used in magnesium dietary supplements. It is also used as an active ingredient in different types of medication. A possible mechanism for the antimicrobial property of MgO NPs is the ability to disrupt membrane integrity and induce oxidative stress to bacterial cells. MgO NPs act as superior antimicrobial substances in the presence of UV light activation. MgO NPs have the advantages of being nontoxic to humans and having simple synthesis protocols. They have good antimicrobial properties against three important foodborne pathogens: Campylobacter jejuni, Salmonella enteritidis, and E. coli. Because of this advantage, they are considered an effective antimicrobial agent in food packaging applications [22]. Titanium dioxide, also known as titanium (IV) oxide or titania, is a naturally occurring ore of titanium (i.e., rutile and anatase). It has been an industrially important chemical since the 18th century and is used as a white pigment and photocatalyst and for UV absorption for different end uses. The free radicals from TiO2 nanoparticles contribute towards its antimicrobial property and hence, it is photodependent. In the presence of UV light excitation, titania has a broad spectrum of bacterial inhibition. The anatase form of titania is has better antimicrobial properties than the rutile form. With this kind of antimicrobial property, titania NPs are used to sterilize medical devices, water, and textile/industrial effluents.

6. Nanocarbon Conventionally, carbon is available in the form of graphite, diamond, and coal. With advances in the field of nanotechnology, various nano-forms of carbon have been exploited for diverse applications, including fullerenes (or bucky ball), CNTs (single-walled or multiwalled), graphene, and diamondoids. Nanocarbon possesses excellent electrical conductivity, mechanical strength, and a surface-to-volume ratio. It is exploited in electronics, composites, biosensors, drug delivery, tissue engineering, fertilizer and pesticide uses, and antimicrobial applications. Fullerenes exhibit antimicrobial property by producing ROS, affecting cellular

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energy metabolism and physical disturbance to the cell membrane. CNTs have a strong electrostatic force of interaction with the microbial outer surface, resulting in oxidation of the membrane. Graphene damages the cell membrane, affects lipid membranes, and induces oxidative stress through ROS generation. The antibacterial activity of diamondoids results from their strong hydrophobicity, which affects the bacterial cell membrane. Apart from physical and chemical effects, synergistic effects are noticed in the antibacterial activity of nanocarbons [23].

7. Other nanomaterials Dendrimers are branched polymers that emerge from a focal point and possess a large number of anionic, cationic, or neutral functionalities on their surface. These materials are in the nanometer dimension and are useful as a delivery or carrier system for drugs and other active ingredients. Although some dendrimers are reported to exhibit antimicrobial properties, they are generally functionalized with various chemicals to exhibit excellent antimicrobial properties. The encapsulation of antibiotics and other nanomaterials in the dendrimeric systems can stabilize and improve their antimicrobial activity in the targeted system. The main targets are to control size, modify the surface of dendrimers, and control the loading of active ingredients into the dendrimers. An example is a ciprofloxacin loaded dendrimer that showed excellent antibacterial activity against S. aureus and Cryptococcus pneumoniae. Similarly, a dendrimer conjugate with erythromycin showed excellent antibacterial activity against S. aureus and S. epidermidis [24]. Liposomes are spherical structures made of a phospholipid bilayer surrounding an inner aqueous space. They range in size from 0.02 to 10 mm [25]. These liposomes are regarded as good carriers for both hydrophilic and hydrophobic therapeutics. Hence, antimicrobial nanomaterials can be loaded in these liposomes for targeted applications. In this case, liposomes support the selective and uniform distribution of application for better antimicrobial properties. Micelles are closed lipid monolayers with a fatty acid core and polar surface. They are conventionally used to deliver of poorly water-soluble drugs. Their size range is generally less than 50 nm. They are used to synthesize or deliver nanomaterials. Nanomicelles are effective nanocarriers for drug delivery owing to their small size, biocompatibility, and capacity to entrap lipophilic drugs. Stimulus-responsive nanomicelles are explored for the release of antimicrobial drugs in response to temperature, pH, light, and other agents [26].

8. Conclusion Nanocrystals are materials with a broad scope for managing microbial problems in various industries. Metals, metal oxides, polymers, and carbon nanomaterials are commercially used to control microbial attack. In addition, dendrimers, liposomes, and micelles are used to deliver antimicrobial nanocrystals efficiently. Coatings on the surface of these nanomaterials could help to avoid the formation of biofilms of microorganisms in industrial establishments

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and biomedical systems. Despite their proven performance, the acceptance of nanocrystals as a microbiocide is limited because of various parameters such as the high cost of production, the lack of facilities for scaling up production of nanocrystals, the unknown level of human toxicity, contamination of the product system, and environmental toxicity.

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The antimicrobial activities of some selected polysaccharide nanocrystals and their hybrids: synthesis and applications Chandan Kumar Sahu1, R. Rashmi1, Jayanth S. Hampapura2 and Ravi-Kumar Kadeppagari1 1

Centre for Incubation, Innovation, Research, and Consultancy, Department of Food Technology, Jyothy Institute of Technology, Tataguni, Bengaluru, Karnataka, India; 2 Department of Microbiology, Yuvaraja’s College, Mysuru, Karnataka, India

1. Introduction A nanocrystal is a particulate material less than 100 nm in size at least in one dimension and that has crystalline properties. Atoms are arranged singly as polycrystalline. The size differentiates them from bigger crystals. Silicon nanocrystals emit light efficiently, whereas larger crystals are used to make memory chips. They exhibit a complex melting behavior when they are incorporated into solids. Quantum dots are semiconducting nanocrystals with dimensions less than 10 nm. The properties of nanocrystals may be explored for different technical applications such as light emission devices, wavelength-adjustable lasers, spintronic equipment, solar cells, and biomedical devices. Zeolite-based nanocrystals were explored to filter crude oil to obtain diesel. This method was cheaper than conventional means. The hardness of nanocrystals is nearer to molecular hardness and it attracts the attention of the wear resistance industry. Antimicrobial compounds have gained attention because of their applications in the sanitary, food packaging, health, and military sectors. Nanoparticles of Ag2Mo2O7 were manufactured in a chitin matrix and showed antibacterial activities [1]. Zinc molybdate crystalline structures inhibited Escherichia coli growth and were manufactured through a hydrothermal method [2]. PbMoO4

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nanocrystals were manufactured through a hydrothermal method by avoiding organic compounds or surfactants and exhibited antibacterial activity [3]. Hence, they can be used in antimicrobial surfaces to make and prepare coatings. They can also be included in polymers used in catheters, implants, and hospital materials. In addition, natural polymers such as chitosan, chitin, starch, and cellulose were used to synthesize nanocrystals. Cellulose nanocrystals (CNCs) were used in antimicrobial food packaging and improved the antimicrobial activities of other materials or composites. In this chapter, we focus on the antimicrobial activities of nanocrystals synthesized from naturally occurring polymers and their hybrids.

2. Biological nanocrystals and their antimicrobial activities 2.1 Cellulose nanocrystals and their hybrids Cellulose is an abundantly available natural polymer. It consists of b-1,4-D-linked glucose chains and has the molecular formula (C6H10O5)n (n is 10,000e15,000). In plant cell walls, around 36 chains of cellulose connect through hydrogen bonding and form elementary fibrils. These pack into larger microfibrils 5e50 nm in diameter and several micrometers long. These microfibrils have amorphous (disordered) and crystalline (ordered) regions. The cellulose chains are closely packed inside crystalline regions through strong intramolecular and intermolecular bonds, whereas they are loosely packed in amorphous regions. These amorphous regions are more vulnerable and selectively hydrolyzed during the mechanical, chemical, or enzymatic treatment of lignocellulosic biomass. Hence, these microfibrils break down into shorter crystalline particles with a higher crystalline nature, called CNCs [4]. CNCs have gained much attention because of their unique characteristics. First, they have nanoscale parameters and good mechanical properties. The Young’s modulus value (167 GPa) of CNCs along the axis of chain is stronger (theoretically) than steel and more or less equal to Kevlar [5]. The elastic modulus for CNCs obtained from tunicate and cotton is around 143 and 105 GPa, respectively [6]. Because CNCs have a high number of OH groups on their surface, surface modification can be achieved with various reactions such as etherification, esterification, silylation, oxidation, and polymer grafting. These reactions functionalize CNCs and help in the dispersion and incorporation of CNCs into various polymer matrices and solvents [4]. Hence, they are designated as standard nano-reinforcement materials for different polymer systems that are water-soluble or insoluble. Reinforced composites are produced by incorporating CNCs into numerous polymers [7,8]. Also, they have environmentally friendly qualities such as renewability, a low energy requirement, biocompatibility, and biodegradability [9]. Because of increased research into the bioconversion of lignocellulosic biomaterials in CNCs and the advantageous chemical and physical properties of CNCs, their polymer nanocomposites have found significant applications in different areas including smart materials, biomedical materials, catalysis, energy, and electronics [10,11]. Various methodologies for synthesizing polymer-based nanocomposites of CNCs were reported [4,12,13]. Many methods focus on materials for conventional films [14]. However, many nonconventional approaches were also reported; important ones are electrospun nanofibers [15,16] and

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CNC-nanocomposite hydrogels [17]. These routes could help expand the applications of natural CNCs for drug delivery, tissue engineering, and medical electronic devices. 2.1.1 Antimicrobial activities of cellulose nanocrystals and their hybrids CNCs and graphene oxide (reduced graphene oxide [rGO]) fabricated through acid hydrolysis and Hummer’s method (modified), respectively, were incorporated into the matrix of poly-lactic acid (PLA) through solution casting. There was an increase (23%) in the tensile strength of the nanocomposite of CNC/rGO/PLA along with an increase in elongation at break (εb), which suggested the ductile characteristic of the composite compared with pristine PLA. Film consisting of a CNC/rGO/PLA nanocomposite had antibacterial efficacy against both gram-negative (E. coli) and gram positive (Staphylococcus aureus) bacteria [18]. In addition, the film had a negligible toxic effect on fibroblast cells in the in vitro cytotoxicity assay. Hence, the synthesized film has significant applications in the biomedical and food packaging sectors. In another approach, ZnO nanoparticles were synthesized within CNCs by in situ solution casting. The nanoparticles of ZnO were dispersed uniformly in the CNC under scanning electron microscopy. After coating with these nanocomposites, the paper had better color stability and exhibited antimicrobial activity against Aspergillus niger, Saccharomyces, Rhizopus nigricans, Aspergillus versicolor, Mucor, E. coli, and S. aureus [19]. CNCs were decorated with iron (spherical) and copper (sheet-like) nanoparticles through oxidation-reduction. The synthesized composite showed efficient antibacterial activity and was efficient in removing Pb2þ [20]. The composites exhibited high antibacterial activity because superoxide radicals damage bacteria irreversibly and lead to apoptosis and the death of bacteria. This composite could remove 94% of the Pb2þ ion and exhibited good reusability (it retained around 80% removal efficiency after six cycles). The process of adsorption followed pseudosecond-order kinetics. This composite may be used for biomedical applications and to treat wastewater. b-Chitosan nanoparticles loaded with lysozyme had enhanced antimicrobial activity against Listeria innocua and E. coli after they were stabilized with CNCs [21]. The CNCs as fillers and stabilizers improved and sustained the antimicrobial activity of these lysozymeloaded chitosan nanoparticles via colloidal stability and electrostatic interactions. This composite may be used in packaging applications to enhance the shelf-life of materials. CNCs grafted with rosin showed moderate antibacterial action against gram-positive bacteria, whereas they had strong action against gram-negative bacteria [22]. CNCs were obtained from pruning the residues of Actinidia deliciosa through bleaching and acidic hydrolysis [23]. Along with carvacrol (active agent), these CNCs were used to reinforce poly vinyl alcohol-chitosan films [23]. The films exhibited antioxidant activity and maintained migration lower than permitted limits. These films also had antibacterial activity, which indicated the protective function of these films and their applications in different industrial sectors and in packaging. A Pickering emulsion of essential oil (oregano) was stabilized by CNCs obtained from microcrystalline cellulose [24]. This emulsion had better stability at high concentrations of CNC and higher pH values, or at a lower salt concentration and oil-to-water ratio. This emulsion could inhibit microbial growth by destroying the integrity of the cell membrane [24]. Bacteriocin of Enterococcus faecium inhibited both gram-positive and gram-negative bacteria. This bacteriocin was immobilized onto CNCs obtained from cotton linters. The immobilization increased (50%) the stability and antimicrobial activity of bacteriocin [25].

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2.2 Starch nanocrystals and their hybrids Starch nanocrystals loaded with b-carotene were incorporated into gelatin-chitosan film using a solution casting method [26]. The gelatin-chitosan film showed decreased swelling, degradation, water solubility, and moisture after starch crystals containing b-carotene were incorporated. Interactions between the starch nanocrystals with b-carotene and chitosangelatin film were revealed in fourier transform infrared spectroscopy (FTIR) analysis. Increased crystallinity was seen in the gelatin-chitosan film during X - ray diffraction (XRD) studies after incorporating the nanocrystals of starch into the film. An uneven surface was observed on the film during scanning electron microscopy (SEM) analysis. The film exhibited radical scavenging activity (90%) in a 2,2-diphenyl-1-picrylhydrazyl assay [26], which suggests strong antimicrobial property for the modified film. The modified film released b-carotene in a sustained manner. Starch nanocrystals were synthesized by the hydrolysis of potato starch with sulfuric acid and were mixed with the extract of sour lemon peel to develop bioactive coating solutions. These solutions may be used to improve the quality of chicken fillets in cold storage [27]. This coating improved the textural, sensory, and physicochemical characteristics of the chicken fillets and exhibited antimicrobial activity against S. aureus, E. coli, Listeria monocytogenes, and Salmonella enterica [27].

2.3 Chitin nanocrystals and their hybrids A study investigated employing chitin nanocrystals in flexible packaging in association with an available coating material [28]. Chitin nanocrystals were oxidized with 2,2,6,6tetramethylpiperidine and applied as a layer in multilayered laminates of biaxially oriented polypropylene (these laminates were bonded by an adhesive acrylic resin). The results illustrated that chitosan nanocrystals improved the O2 barrier characteristic of these laminates [28]. In another study, electrospinning was used to synthesize nanofibers in which PLA was the core and polyacrylonitrile/chitin nanocrystals or polyacrylonitrile/cellulose nanocrystals were the shell [29]. They were prepared at various concentrations of nanocrystals and used as microfiltration membranes. They exhibited a maximum pore size of 1.2e2.6 mm and rejected more than 85% of bacterial cells (0.5  2.0 mm) and greater than 99% of fungal spores (>2 mm). The fibers were bead-less with clear core/shell structures and showed the presence of ultrafine secondary fibers. The permeability of water increased with all membranes containing nanocrystals. The highest corresponded to films containing chitosan nanocrystals (240%). Membranes with CNCs were hydrophilic and those with chitosan nanocrystals were superhydrophilic. The charge on the surface of CNC membranes was negative, whereas that on the chitosan nanocrystal-incorporated membranes was positive or neutral (owing to chitin units that are deacetylated). The chitosan nanocrystal-containing membranes had high antimicrobial activity in cultures of E. coli, and bacteria could not colonize under favorable biofilm-forming conditions [29].

3. Inorganic nanocrystals and their antimicrobial activities PbMoO4 nanocrystals were synthesized through a hydrothermal method and had a tetragonal structure (scheelite-type) without secondary phases. The PbMoO4 nanocrystals exhibited VII. Antibacterial and antifungal coatings

References

333

a minimal inhibitory concentration (MIC) of 1024 mg mL1 against the strains of bacteria [3]. They exhibited a synergic effect with gentamicin against S. aureus. However, during assays against gram-negative bacteria, an antagonistic effect was observed because lead present in nanocrystals affected the antibiotic. Nanocrystals of CuO were synthesized by a wet chemical process using hexamethylenetetramine and copper acetate as precursor materials [30]. These nanocrystals exhibited antimicrobial activity against E. coli and the MIC was measured at 2.5 mg mL1. The transmission electron microscopy (TEM) results indicated that these nanocrystals irreversibly damaged the cell wall and caused cell death. The mesoporous bioactive glass (MBG) was synthesized by spray pyrolysis and silver nanoparticles were reduced on it by synchrotron X-ray irradiation [31]. The Ag-MBG powder showed the even distribution of Ag nanoparticles and higher antimicrobial activity against E. coli and S. aureus [31]. Very little literature is available on the antimicrobial properties of nanocrystals, and there is more scope for research focused on their applications.

References [1] H. Tang, A. Lu, L. Li, W. Zhou, Z. Xie, L. Zhang, Highly antibacterial materials constructed from silver molybdate nanoparticles immobilized in chitin matrix, Chem. Eng. J. 234 (2013) 124e131. [2] C.C. Mardare, D. Tanasic, A. Rathner, N. Muller, A.W. Hassel, Growth inhibition of Escherichia coli by zinc molybdate with different crystalline structures, Phys. Status Solidi 213 (2016) 1471e1478. [3] J.V.B. Moura, T.S. Freitas, A.R.P. Silva, A.T.L. Santos, J.H. da Silva, R.P. Cruz, R.L.S. Pereira, P.T.C. Freire, C. Luz-Lima, G.S. Pinheiro, H.D.M. Coutinho, Synthesis, characterizations, and antibacterial properties of PbMoO4 nanocrystals, Arab. J. Chem. 11 (2018) 739e746. [4] Y. Habibi, L.A. Lucia, O.J. Rojas, Cellulose nanocrystals: chemistry, self-assembly, and applications, Chem. Rev. 110 (2010) 3479e3500. [5] K. Tashiro, M. Kobayashi, Theoretical evaluation of three-dimensional elastic-constants of native and regenerated celluloses: role of hydrogen-bonds, Polymer 32 (1991) 1516e1530. [6] A. Sturcova, G.R. Davies, S.J. Eichhorn, Elastic modulus and stress-transfer properties of tunicate cellulose whiskers, Biomacromolecules 6 (2005) 1055e1061. [7] I. Kvien, B.S. Tanem, K. Oksman, Characterization of cellulose whiskers and their nanocomposites by atomic force and electron microscopy, Biomacromolecules 6 (2005) 3160e3165. [8] X.D. Cao, Y. Habibi, W.L.E. Magalhaes, O.J. Rojas, L.A. Lucia, Cellulose nanocrystals-based nanocomposites: fruits of a novel biomass research and teaching platform, Curr. Sci. 100 (2011) 1172e1176. [9] I. Siro, D. Plackett, Microfibrillated cellulose and new nanocomposite materials: a review, Cellulose 17 (2010) 459e494. [10] A.P. Mangalam, J. Simonsen, A.S. Benight, Cellulose/DNA hybrid nanomaterials, Biomacromolecules 10 (2009) 497e504. [11] N. Duran, A.P. Lemes, M. Duran, J. Freer, J. Baeza, A minireview of cellulose nanocrystals and its potential integration as Co-product in bioethanol production, J. Chil. Chem. Soc. 56 (2011) 672e677. [12] S.J. Eichhorn, Cellulose nanowhiskers: promising materials for advanced applications, Soft Matter 7 (2011) 303e315. [13] R.J. Moon, A. Martini, J. Nairn, J. Simonsen, J. Youngblood, Cellulose nanomaterials review: structure, properties and nanocomposites, Chem. Soc. Rev. 40 (2011) 3941e3994. [14] B.L. Peng, N. Dhar, H.L. Liu, K.C. Tam, Chemistry and applications of nanocrystalline cellulose and its derivatives: a nanotechnology perspective, Can. J. Chem. Eng. 89 (2011) 1191e1206. [15] O.J. Rojas, G.A. Montero, Y. Habibi, Electrospun nanocomposites from polystyrene loaded with cellulose nanowhiskers, J. Appl. Polym. Sci. 113 (2009) 927e935. [16] M. Martinez-Sanz, R.T. Olsson, A. Lopez-Rubio, J.M. Lagaron, Development of electrospun EVOH fibres reinforced with bacterial cellulose nanowhiskers. Part I: characterization and method optimization, Cellulose 18 (2011) 335e347.

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[17] K. Shanmuganathan, J.R. Capadona, S.J. Rowan, C. Weder, Bio-inspired mechanically-adaptive nanocomposites derived from cotton cellulose whiskers, J. Mater. Chem. 20 (2010) 180e186. [18] N. Pal, P. Dubey, P. Gopinath, K. Pal, Combined effect of cellulose nanocrystal and reduced graphene oxide into poly-lactic acid matrix nanocomposite as a scaffold and its anti-bacterial activity, Int. J. Biol. Macromol. 95 (2017) 94e105. [19] M. Jia, X. Zhang, J. Weng, J. Zhang, M. Zhang, Protective coating of paper works: ZnO/cellulose nanocrystal composites and analytical characterization, J. Cult. Herit. 38 (2019) 64e74. [20] L. Chen, H. Yu, C. Deutschman, T. Yang, K.C. Tam, Novel design of Fe-Cu alloy coated cellulose nanocrystals with strong antibacterial ability and efficient Pb2þ removal, Carbohydr. Polym. 234 (2020) 115889. [21] H. Zhang, M. Feng, S. Chen, W. Shi, X. Wang, Incorporation of lysozyme into cellulose nanocrystals stabilized b-chitosan nanoparticles with enhanced antibacterial activity, Carbohydr. Polym. 236 (2020) 115974. [22] D.O. Castro, J. Bras, A. Gandini, N. Belgacem, Surface grafting of cellulose nanocrystals with natural antimicrobial rosin mixture using a green process, Carbohydr. Polym. 137 (2016) 1e8. [23] F. Luzi, E. Fortunati, G. Giovanale, A. Mazzaglia, L. Torre, G.M. Balestra, Cellulose nanocrystals from Actinidia deliciosa pruning residues combined with carvacrol in PVA_CH films with antioxidant/antimicrobial properties for packaging applications, Int. J. Biol. Macromol. 104 (2017) 43e55. [24] Y. Zhou, S. Sun, W. Bei, M. Reda, Z. Qipeng, Y.H. Liang, Preparation and antimicrobial activity of oregano essential oil Pickering emulsion stabilized by cellulose nanocrystals, Int. J. Biol. Macromol. 112 (2018) 7e13. [25] P. Bagde, V. Nadanathangam, Improving the stability of bacteriocin extracted from Enterococcus faecium by immobilization onto cellulose nanocrystals, Carbohydr. Polym. 209 (2019) 172e180. [26] N. Hari, S. Francis, A.G.R. Nair, A.J. Nair, Synthesis, characterization and biological evaluation of chitosan film incorporated with b-Carotene loaded starch nanocrystals, Food Packag. Shelf Life 16 (2018) 69e76. [27] Z. Alizadeh, S. Yousefi, H. Ahari, Optimization of bioactive preservative coatings of starch nanocrystal and ultrasonic extract of sour lemon peel on chicken fillets, Int. J. Food Microbiol. 300 (2019) 31e42. [28] T. Zhong, M.P. Wolcott, H. Liu, J. Wang, Developing chitin nanocrystals for flexible packaging coatings, Carbohydr. Polym. 226 (2019) 115276. [29] B. Jalvo, A.P. Mathew, R. Rosal, Coaxial poly (lactic acid) electrospun composite membranes incorporating cellulose and chitin, J. Membr. Sci. 544 (2017) 261e271. [30] M.S. Hassan, T. Amna, O.-B. Yang, M.H. El-Newehy, S.S. Al-Deyab, M.-S. Khil, Smart copper oxide nanocrystals: synthesis, characterization, electrochemical and potent antibacterial activity, Colloids Surf. B Biointerfaces 97 (2012) 201e206. [31] F.-Y. Fan, M.-S. Chen, C.-W. Wang, S.-J. Shih, C.-Y. Chen, Y.-N. Pan, C.-K. Lin, Preparation and characterization of silver nanocrystals decorated mesoporous bioactive glass via synchrotron X-ray reduction, J. Non-Cryst. Solids 450 (2016) 128e134.

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C H A P T E R

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Applications of biogenic silver nanocrystals or nanoparticles as bactericide and fungicide Aruna Jyothi Kora1, 2 1

National Centre for Compositional Characterisation of Materials, Bhabha Atomic Research Centre, ECIL PO, Hyderabad, Telangana, India; 2Homi Bhabha National Institute, Mumbai, Maharashtra, India

1. Introduction Silver nanocrystals or nanoparticles are synthesized from an array of biogenic sources such as plant leaves [1,2], roots, stems, fruits [3], and seeds [4,5]; tree gum [6e8]; bacteria [9,10]; fungi [11,12]; algae [13,14]; and biomolecules [15]. Biogenic sources are preferred compared with chemical synthesis owing to their renewability, low cost, nontoxicity, biodegradability, biocompatibility, the tunability of the size and shape of nanocrystals, and their dual ability to function as reductant and stabilizer molecules [16,17].

2. Characterization techniques for silver nanoparticles Green synthesized silver nanoparticles (Ag NP) are characterized by a range of analytical instrumental techniques such as UV-visible absorption spectroscopy (UV-vis), x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. These methods will aid in an understanding of the various aspects of nanoparticle formation, their physical and chemical properties, and their biological activity. UV-vis is an easy and powerful tool for studying and characterizing Ag NP and other metal nanoparticles, because they are strongly absorbed in the visible to infrared region in the form of a typical surface plasmon resonance (SPR) peak and coloration of the produced nanoparticles [7]. TEM is employed to find the size, shape, morphology, and arrangement of

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nanomaterials [5]. XRD is an important fingerprint characterization technique widely used to derive the crystal structure and geometry of nanomaterials [6]. FTIR deals with the characteristic vibration spectroscopy of atoms in a molecule. It is employed to study the functional groups of biomolecules that contribute to the biosynthesis and stabilization of Ag NP [8]. Raman spectroscopy is a molecular fingerprinting technique that is complementary to infrared spectroscopy. It is used to study the vibrational and rotational frequency modes of a system and enables the detection of molecules and their functional groups, providing chemical and structural information. It is employed to determine the probable functional groups of capping molecules associated with the stabilization of Ag NP [8]. These methods will help in an understanding of the various aspects of nanoparticle formation, their physical and chemical properties, and their biological activity.

3. Biogenic synthesis of silver nanoparticles Ag NP with a size of 17.5 nm were biosynthesized at room temperature for 2 h using a 0.4% leaf extract of Dendrophthoe falcata with 1 mM silver nitrate (AgNO3) (Ag NP-DF) [1]. The seed extract (0.5%) of Strychnos potatorum was used for the biogenic synthesis of Ag NP (14.1 nm in size) by autoclaving for 30 min at 121
C and 103 kPa (Ag NP-SP) [8]. An array of plant and tree exudate gums, such as kondagogu (Cochlospermum gossypium), ghatti (Anogeissus latifolia), olibanum (Boswellia serrata), tragacanth (Astragalus gummifer), arabic (Acacia arabica), and karaya (Sterculia urens), were used for the biosynthesis of Ag NP. The Ag NP of 4.5 nm were produced by 0.5% of gum kondagogu and 1 mM AgNO3 by autoclaving for 60 min (Ag NP-KG) [7]. For gum ghatti, Ag NP of 5.7 nm was autoclave-synthesized at 0.1% gum concentration, 1 mM AgNO3 at 30 min (Ag NP-GT) [6]. With gum olibanum, 7.5 nm Ag NP was achieved with 0.5% gum and 1 mM AgNO3 by autoclaving for 30 min (Ag NP-OB) [6,18]. The 13.1-nm Ag NP of size were biosynthesized with gum tragacanth by autoclaving for 30 min at 0.1% gum and 1 mM AgNO3 (Ag NP-TG) [8]. The Ag NP of 21.6 nm were biofabricated with xanthan gum produced by the bacterium Xanthomonas campestris at 0.1% gum and 1 mM AgNO3 by autoclaving for 20 min (Ag NP-XG) [19]. The UVvis spectra of various Ag NP biosynthesized with D. falcata leaf extract, S. potatorum seed extract, gum kondagogu, gum ghatti, gum olibanum, gum tragacanth, and xanthan gum, labeled as Ag NP-DF, Ag NP-SP, Ag NP-KG, Ag NP-GT, Ag NP-OB, Ag NP-TG, and Ag NP-XG, exhibited SPR peaks at 430, 414, 408, 415, 418, 418, and 446 nm, respectively (Fig. 18.1A). The colorations of the produced Ag NP solutions are given in Fig. 18.1B. They indicate a range of typical faint yellow, yellow, dark yellow, faint brown, brown, and dark brown characteristic of Ag NP. The TEM images of Ag NP-DF, Ag NP-SP, Ag NP-KG, Ag NP-GT, Ag NP-OB, Ag NP-TG, and Ag NP-XG are mostly spherical and quasispherical; average particle sizes were about 17.5, 14.1, 4.5, 5.7, 7.5, 13.1, and 21.6 nm, respectively (Fig. 18.2). The XRD pattern of biogenic Ag NP synthesized with a culture filtrate of bacterium Pseudomonas aeruginosa showed a typical face-centered cubic crystal structure of elemental silver, which was evident from the (111), (200), (220), and (311) lattice planes (Fig. 18.3A). The FTIR spectrum of Ag NP-SP indicated the involvement of hydroxyl and carbonyl groups, and proteins of the seed extract in the biosynthesis and stabilization of

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FIGURE 18.1 (A) UV-visible spectroscopy absorption spectra of various biogenic Ag nanoparticles (Ag NP) showing surface plasmon resonance peaks. (B) Colors of produced Ag NP solutions.

FIGURE 18.2 Transmission electron microscopy images of (A) Ag nanoparticles (NP)-DF, (B) Ag NP-SP, (C) Ag NP-KG, (D) Ag NP-GT, (E) Ag NP-OB, (F) Ag NP-TG, and (G) Ag NP-XG.

FIGURE 18.3 (A) X-ray diffraction pattern of biogenic Ag nanoparticles (NP) synthesized with culture filtrate of bacterium Pseudomonas aeruginosa. (B) Fourier transform infrared spectroscopy spectrum of Ag NP-SP. (C) Raman spectrum of Ag NP-SP. VII. Antibacterial and antifungal coatings

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Ag NP (Fig. 18.3B). The participation of proteins in the capping and stabilization of Ag NPSPs was confirmed by the Raman spectrum (Fig. 18.3C). In view of these findings, a list of selected biogenic sources employed for the green synthesis of Ag NP is given in terms of their scientific names, the reductants involved in synthesis, and the particle size (Table 18.1). Biogenic Ag NP exhibit biocidal activity against various bacteria and fungi, and thus function as bactericides and fungicides. The myriad applications of Ag NP are accounted for by their minute particle size and higher surface area. Biogenic Ag NP are used as antibacterials, antibiofilms, cytotoxic agents, bactericides [28], fungicides [29], nanocatalysts [19], and visual mercury sensors [30]. TABLE 18.1

Biogenic Ag nanoparticle scientific names, reductants, and particle sizes.

Scientific name

Reductant

Ag nanoparticle size/size range (nm)

Reference

Delftia sp.

Cell-free supernatant

9.8

[10]

Alternaria alternata

Extracellular cell filtrate

32.5

[12]

Stenotrophomonas sp.

Culture supernatant

12

[20]

Aspergillus terreus

Culture supernatant

5e30

[11]

Padina pavonica

Thallus broth

54

[13]

Hypnea musciformis

Thallus broth

16e42

[14]

Ulva fasciata

Thallus extract

40

[21]

Dendrophthoe falcata

Leaf extract

17.5

[1]

Acalypha indica

Leaf extract

20e30

[2]

Pedalium murex

Leaf extract

50

[22]

Cassia roxburghii

Leaf extract

35

[23]

Centella asiatica

Leaf extract

28.4

[24]

Strychnos potatorum

Seed extract

14.1

[5]

Sinapis arvensis

Seed extract

14

[4]

Cochlospermum gossypium

Exudate gum

4.5

[7]

Anogeissus latifolia

Exudate gum

5.7

[6]

Boswellia serrata

Exudate gum

7.5

[6,18]

Astragalus gummifer

Exudate gum

13.1

[8]

Acacia arabica

Exudate gum

35

[25]

Sterculia urens

Exudate gum

2e4

[26]

Anacardium occidentale

Exudate gum

4

[27]

Xanthomonas campestris

Extracellular gum

21.6

[19]

Streptomyces sp.

Amphotericin B

7

[15]

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4. Applications of Ag nanoparticles as bactericide The antibacterial actions of Ag NP were extensively studied against different bacteria, such as environmental bacteria and human, foodborne, waterborne, and plant pathogens. The list includes Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus [31], Bacillus subtilis, Bacillus pumilus, Micrococcus flavus, Klebsiella pneumoniae [22], Pectobacterium carotovorum, Ralstonia solanacearum, Erwinia amylovora, Xanthomonas citri [3], Vibrio cholera [2], Micrococcus luteus, Klebsiella planticola [32], Xanthomonas oryzae [33], Acinetobacter baumannii, Mycobacterium smegmatis, Mycobacterium bovis [34], Pseudomonas syringae [35], Microcystis aeruginosa [36], Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus faecalis, Salmonella typhus [27], Xanthomonas campestris [21], Xanthomonas axonopodis [37], and Ralstonia solanacearum [14]. Diverse in vitro and in vivo methods including disc diffusion, agar well diffusion, broth dilution, crystal violet antibiofilm activity, and growth kinetic assays are used to study the susceptibility of an array of bacteria toward Ag NP [28,31]. The antibacterial action of Ag NP-DF against different bacterial strains is studied with the well diffusion assay. Notable inhibition zones at 5 mg are shown in Fig. 18.4 [1]. The values of inhibition zones recorded with various biogenic Ag NP against the test bacterial strains P. aeruginosa, E. coli (Gram negative) and S. aureus (Gram positive) are listed in Table 18.2. The results demonstrate the considerable antibacterial action of biogenic Ag NP on both Gram classes of bacteria, which was higher than reported values [38]. The minimum inhibitory concentration (MIC) values of various biogenic Ag NP against different bacterial strains were determined with broth dilution and compared with respect to the particle size and bacterial strain (Table 18.3). Biogenic Ag NP synthesized using tree gum were more powerful bactericidal agents with respect to the concentration [32]. The inhibition of biofilm development by biogenic Ag NP was probed with static microtiter plate assay at 2 mg mL1 concentration (Table 18.4). The NP hindered biofilm development and showed nearly similar antibiofilm activity toward the test strains. The growth kinetics of P. aeruginosa ATCC 27583 and S. aureus ATCC 25923 bacterial strains

FIGURE 18.4

Well diffusion assay at 5 mg of Ag nanoparticle (NP)-DF against different bacterial strains.

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TABLE 18.2

Inhibition zones (mm) observed with different bacterial culture plates loaded with 5 mg of biogenic Ag nanoparticles (Ag NP) in well diffusion assay. Escherichia coli ATCC 25922

Escherichia coli ATCC 35218

Staphylococcus aureus ATCC 25923

Ag NP-KG 8.7  0.1

8.0

8.4

11.0  0.1

Ag NP-GT

11.0

9.0

8.0  0.1

12.2  0.2

Ag NP-OB

7.5

8.0  1.0

5.5

10.7  0.2

Ag NP-TGC 10.5

9.5  0.4

5.5

11.5

Ag NP-DF

6.0

7.0

14.0

Biogenic Ag NP

Pseudomonas aeruginosa ATCC 27853

18.0

TABLE 18.3

Minimum inhibitory concentrations (MIC) values noted with biogenic Ag nanoparticles against different bacterial strains, in terms of particle size and bacterial strain.

Bacterial strain

MIC (mg mLL1)

Particle size (nm)

Reference

Escherichia coli

2

4.5

[28]

E. coli

10

20e30

[2]

E. coli

32

13

[32]

E. coli

6.7

4

[27]

Pseudomonas aeruginosa

5

5.7

[31]

P. aeruginosa

3.3

4

[27]

P. aeruginosa

16

13

[32]

Klebsiella pneumoniae

6.7

4

[27]

Klebsiella planticola

16

13

[32]

Vibrio cholerae

10

20e30

[2]

Xanthomonas campestris

40

40

[21]

Staphylococcus aureus

10

7.5

[31]

S. aureus

13.5

4

[27]

S. aureus

32

13

[32]

Staphylococcus epidermidis

3.3

4

[27]

Micrococcus luteus

8

13

[32]

Enterococcus faecalis

13.5

4

[27]

Bacillus subtilis

16

13

[32]

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TABLE 18.4

Biofilm inhibition by biogenic Ag nanoparticles (Ag NP) and antibiotic ciprofloxacin toward different bacterial strains. Biofilm inhibition (%)

Test compound (mg mLL1)

Staphylococcus aureus ATCC 25923

Pseudomonas aeruginosa ATCC 27583

Escherichia coli ATCC 25922

Escherichia coli ATCC 35218

Ag NP-KG (2)

66.3  1.3

73.7  0.3

83.9  0.2

93.1  0.4

Ag NP-GT (2)

64.5  3.5

78.7  0.8

81.1  1.5

92.9  0.4

Ag NP-OB (2)

61.4  0

77.0  1.6

82.9  0.4

92.9  0.4

Ciprofloxacin (0.1) 73.0  0

39.4  3.5

83.1  0

93.3  0.6

FIGURE 18.5 Growth curve of (A) Pseudomonas aeruginosa ATCC 27583 and (B) Staphylococcus aureus ATCC 25923 bacterial strains treated with 10 mg mL1 of gum synthesized Ag nanoparticles (NP), comparison with untreated control.

were checked in nutrient broth supplemented with 10 mg mL1 of gum-synthesized Ag NP for 48 h at 600 nm (Fig. 18.5). At the tested concentration, all Ag NP completely arrested the growth curve of P. aeruginosa, compared with untreated bacteria. In gram-positive S. aureus, Ag NP-GT and Ag NP-OB caused the complete inhibition of cell division at 10 mg mL1. The results of various bactericidal assays indicate the dependence of bacterial growth inhibition on the bacterial strain type, particle size, and concentration of the Ag NP. Biogenic Ag NP synthesized with tree gum are protein-capped and have enhanced bactericidal action [28,31]. The strong antibacterial action of biogenic Ag NP results from the excellent stability of the nanoparticle solutions. Biogenic Ag NP exhibit higher stability toward variable pH, salt concentrations, elevated temperatures, and storage conditions [7,25,30,39].

5. Mechanism of bactericidal action of biogenic Ag nanoparticles The mechanism of biocidal action was studied with different assays to detect cytoplasmic leaks, membrane destabilization, and reactive oxygen species (ROS) production. Membrane

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damage in terms of the leak of cytoplasmic contents (nucleic acids and proteins) was studied by recording UV absorbance at 260 and 280 nm. Nucleic acid and protein release with E. coli ATCC 25922 and P. aeruginosa ATCC 27853 strains at 2 and 5 mg mL1 concentration of gumreduced Ag NP, respectively, are given in Fig. 18.6. The outer membrane of gram-negative bacteria functions as a permeability barrier and excludes hydrophobic, fluorescent probe N-phenyl naphthylamine (NPN). Because of the destabilizing action of Ag NP, the entry of NPN into the outer membrane of the phospholipid layer results in typical fluorescence. The dose-dependent outer membrane breakage of Ag NP-treated E. coli 25922 and P. aeruginosa 27853 compared with positive control hydrogen peroxide is given in Fig. 18.7. The participation of ROS in the antibacterial action of Ag NP was demonstrated via an antioxidant assay. The antioxidant N-acetyl cysteine (NAC) was employed as a scavenger

FIGURE 18.6 Leakage of (A) nucleic acids in Escherichia coli 25922 and (B) proteins in Pseudomonas aeruginosa 27853 treated with 2 and 5 mg mL1 of gum-reduced Ag nanoparticles (Ag NP).

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FIGURE 18.7 Outer membrane damage of Ag nanoparticles (Ag NP) treated with (A) Escherichia coli 25922 and (B) Pseudomonas aeruginosa 27853, compared with positive control hydrogen peroxide.

for ROS produced by Ag NP. The percent survival of various bacterial strains in media supplemented with NAC and Ag NP is shown in Fig. 18.8. At a concentration of 5 mg mL1 of NP (Ag NP-KG, Ag NP-GT, and Ag NP-OB), bacterial growth was completely inhibited. The supplementation of NAC caused bacterial cell recovery at different levels (37.1e100%) from the bactericidal action of Ag NP. The findings support free radical generation from the Ag NP surface and involvement in bacterial growth inhibition. The indication of cellular oxidative stress in terms of intracellular ROS generation was monitored with fluorescent dye dichlorodihydrofluorescein diacetate. The response of bacterial strains P. aeruginosa 27853 and S. aureus 25923 toward Ag NP (2 mg mL1) is shown with respect to ROS production, compared with the positive control hydrogen peroxide (Fig. 18.9). Intracellular ROS production during Ag NP interaction with bacteria confirms the role of oxidative stress in Ag NP toxicity.

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FIGURE 18.8 Percent survival of various bacterial strains in the presence of N-acetyl cysteine (NAC) and 5 mg mL1 of Ag nanoparticles (Ag NP).

FIGURE 18.9 Production of intracellular reactive oxygen species in (A) Pseudomonas aeruginosa 27853 and (B) Staphylococcus aureus 25923 treated with 2 mg mL1 of Ag nanoparticles (Ag NP), compared with positive control hydrogen peroxide.

The effect of gum-synthesized Ag NP (5 mg mL1) on gram-positive S. aureus cell surface morphology was investigated using scanning electron microscopy (Fig. 18.10). Spherical S. aureus cells were clearly visible in the untreated sample. After Ag NP interaction, most cells were severely affected and disappeared. The electron micrographs indicate NP attachment to the bacterial cell surface and structural damage to the cell surface. Ag NP interaction with bacteria and the mechanism of biocidal action are schematically exemplified via membrane damage and ROS production (Fig. 18.11). Based the data, it is thought that ROS may be produced from the Ag NP surface, act toward the cell wall and membrane, destabilize the cell membrane, enhance cell porosity, and release intracellular proteins and nucleic acids via cell disruption. Furthermore, bacterial interaction with NP leads to structural and

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FIGURE 18.10 Scanning electron microscopy photographs of Staphylococcus aureus 25923 cells at 200-nm scale (A) before; and after treatment with 5 mg mL1 of (B) Ag nanoparticles (Ag NP)-KG, (C) Ag NP-GT, and (D) Ag NPOB.

FIGURE 18.11 Schematic indicating the interaction of Ag nanoparticles (Ag NP) with bacteria and the mechanism of antibacterial action.

morphologic alterations and cell surface damage. Thus, the findings confirm the involvement of ROS and cell membrane damage in the antibacterial activity of biogenic Ag NP. Nevertheless, future studies are required to probe the complex mechanism(s) associated with the bactericidal action of Ag NP.

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18. Applications of biogenic silver nanocrystals or nanoparticles as bactericide and fungicide

6. Applications of Ag nanoparticles as fungicides Biogenic Ag NP show antifungal action against a broad spectrum of fungi such as human pathogens, dermatophytes, foodborne pathogens, plant pathogens, and wood-degrading fungi. The list includes Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, Trichophyton mentagrophytes [40], Saccharomyces cerevisiae [41], Phoma glomerata, Phoma herbarum, Fusarium semitectum, Trichoderma sp. [12], Bipolaris sorokiniana, Magnaporthe grisea [42], Raffaelea sp. [43], Rhizoctonia solani [29], Sclerotinia sclerotiorum, Sclerotinia minor [44], Sclerotium cepivorum [45], Sclerotium rolfsii [46], Aspergillus flavus, Alternaria alternata [47], Macrophomina phaseolina, Botrytis cinerea, Curvularia lunata [48], Gloeophyllum abietinum, Gloeophyllum trabeum, Chaetomium globosum, Phanerochaete sordida [49], Neofusicoccum parvum [4], Penicillium brevicompactum, Aspergillus fumigatus, Cladosporium cladosporioides, Chaetomium globosum, Stachybotrys chartarum, Mortierella alpina [50], Fusarium oxysporum [51], Aspergillus niger [23], Alternaria citri, Penicillium digitatum [52], Fusarium culmorum [15], Cladosporium fulvum [53], Aspergillus versicolor, Aspergillus tamarii [54], Alternaria solani [55], Aspergillus parasiticus [56], Phytophthora capsici, and Colletotrichum acutatum [57]. The fungicidal activity of biogenic Ag NP was studied with various methods including disc diffusion, poisoned food, conidial germination, sclerotia germination, resazurin broth, and the detached leaf assay [29]. The fungicidal action of rice leaf extract synthesized Ag NP was studied with poisoned food against the mycelial disc of phytopathogen Rhizoctonia solani and complete radial growth inhibition was observed at 10 mg mL1 compared with control (Fig. 18.12A). The MIC of Ag NP was determined by resazurin broth assay. The color transformation into fluorescent pink and purple indicated viable and nonviable mycelia, respectively. Culture tubes inoculated with mycelial discs of R. solani became purple at an MIC of 10 mg mL1 of Ag NP compared with the pink untreated tube (Fig. 18.12B). The antifungal action of the biogenic Ag NP was compared with respect to fungal pathogens, hyphal growth inhibition, nanoparticle size, and concentration (Table 18.5).

7. Other antimicrobial applications of Ag nanoparticles The antimicrobial spectrum of Ag NP is used in various industrial and consumer sectors such as antibacterial food packaging materials [61], absorbent pads [62], Ag NP-embedded agar films [63], Ag NP-incorporated alginate edible coatings [64], celluloseeAg NP composites [65], cosmetic preservatives [66], antibacterial coatings [67], Ag NP-decorated water FIGURE 18.12 Fungicidal action of rice leaf extract-synthesized Ag nanoparticles at (i) 0 and (i) 10 mg mL1 concentration against the mycelial disc of phytopathogen Rhizoctonia solani in (A) poisoned food and (B) resazurin broth assay.

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8. Conclusions

TABLE 18.5

Comparison of noted hyphal growth inhibition in various fungal pathogens treated with biogenic Ag nanoparticles.

Fungal strain

Particle size (nm) Concentration (mg mLL1)

Hyphal growth inhibition (%) References

Alternaria alternata

10e20

100

60

[47]

Alternaria citri

10

150

81.1

[52]

Aspergillus flavus

5e30

150

100

[11]

Aspergillus niger

60

50

70

[58]

Aspergillus parasiticus

3.6

6.5

100

[56]

Cladosporium fulvum

16.7

200

55.5

[53]

Cladosporium cladosporioides

60

50

90

[58]

Colletotrichum sp.

4e8

100

52.6e100

[59]

Fusarium oxysporum

23

1500

86

[51]

Magnaporthe grisea

20e30

200

72.8

[60]

Neofusicoccum parvum

14

40

83

[4]

Penicillium digitatum

10

150

78.8

[52]

Raffaelea sp.

4e8

25

12

[43]

Rhizoctonia solani

16.5

10

82e97

[29]

Sclerotium rolfsii

300e350

750

100

[46]

Sclerotinia sclerotiorum

4e8

7

64

[44]

filters, antibacterial air filters [68], antifouling membranes [69], antibacterial surgical masks, Ag NP-coated medical devices, nano-silver impregnated catheters [70], surgical sutures, antimicrobial wound dressings, Ag NP-coated textile fabrics, antibacterial creams and gels, antimicrobial nano paint [71], silver bone cement [72], orthodontic adhesives [73], silverdispersed carbon aerogels [74], antibacterial stainless steel [75], antibacterial Ag NP-coated glass [76], and antibacterial ceramics [77].

8. Conclusions Ag NP biosynthesized from an array of biological sources offer many advantages in terms of green chemistry principles. Solutions of Ag NP exhibit typical coloration, SPR peaks in UVvis absorption spectra, and a face-centered cubic crystal structure. The morphologic size and shape of nanocrystals can be tuned by the reaction conditions. Protein-capped biogenic Ag NP have superior stability and function as bactericides and fungicides against a broad spectrum of bacteria and fungi, respectively. The nanobiocide action of Ag NP were studied extensively using different methods against environmental microbes and human, plant,

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18. Applications of biogenic silver nanocrystals or nanoparticles as bactericide and fungicide

waterborne, and foodborne pathogens. The antibacterial action of Ag NP is attributed to membrane damage and ROS production. The antimicrobial action of Ag NP is exploited in various industrial, commercial, and biomedical sectors. In addition to consumer acceptance, extensive studies on cytotoxicity and genotoxicity are needed for different nontarget biota in the food web.

Acknowledgments The author would like to thank Dr. M.V. Balarama Krishna, head of the Environmental Science and Nanomaterials Section, and Dr. Sanjiv Kumar, head of National Centre for Compositional Characterization of Materials, Bhabha Atomic Research Centre, for their constant support and encouragement throughout the work.

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[72] V. Alt, T. Bechert, P. Steinrucke, M. Wagener, P. Seidel, E. Dingeldein, R. Schnettler, An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement, Biomaterials 25 (18) (2004) 4383e4391, https://doi.org/10.1016/j.biomaterials.2003.10.078. [73] S.J. Ahn, S.J. Lee, J.K. Kook, B.S. Lim, Experimental antimicrobial orthodontic adhesives using nanofillers and silver nanoparticles, Dent. Mater. 25 (2) (2009) 206e213, https://doi.org/10.1016/j.dental.2008.06.002. [74] S. Zhang, R. Fu, D. Wu, W. Xu, Q. Ye, Z. Chen, Preparation and characterization of antibacterial silver-dispersed activated carbon aerogels, Carbon 42 (15) (2004) 3209e3216, https://doi.org/10.1016/j.carbon.2004.08.004. [75] L. Chen, L. Zheng, Y. Lv, H. Liu, G. Wang, N. Ren, R.I. Boughton, Chemical assembly of silver nanoparticles on stainless steel for antimicrobial applications, Surf. Coating. Technol. 204 (23) (2010) 3871e3875, https://doi.org/ 10.1016/j.surfcoat.2010.05.003. [76] N. Perkas, G. Amirian, G. Applerot, E. Efendiev, Y. Kaganovskii, A.V. Ghule, A. Gedanken, Depositing silver nanoparticles on/in a glass slide by the sonochemical method, Nanotechnology 19 (43) (2008) 435604, https://doi.org/10.1088/0957-4484/19/43/435604. [77] V. Bakumov, K. Gueinzius, C. Hermann, M. Schwarz, E. Kroke, Polysilazane-derived antibacterial silvere ceramic nanocomposites, J. Eur. Ceram. Soc. 27 (10) (2007) 3287e3292, https://doi.org/10.1016/ j.jeurceramsoc.2007.01.004.

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Crystalline nanomaterials for antimicrobial applications Deepika S. Brijpuriya1, Dilip R. Peshwe2 and Anupama Kumar3 1

Postgraduate Department of Chemistry, Santaji Mahavidyalaya, Nagpur, Maharashtra, India; 2 Department of Metallurgical and Materials Engineering, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, India; 3Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, India

1. Introduction The use of nanotechnology in various sectors of therapeutics has revolutionized the field of medicine, for which nanoparticles (1e100 nm) are designed and used for diagnostics, therapeutics, and as biomedical tools for research [1]. Emerging infectious diseases and increase in the incidence of drug resistance in the pathogenic bacteria have made the search for new antimicrobials inevitable. One of the most promising and novel therapeutics agents is nanocrystals [2]. Nanocrystals are nanosized molecules with large surface area to volume ratio, which helps them to penetrate bacterial cells easily. Nanoparticles possess unique physicochemical, optical, and biological properties that can be manipulated suitably for desired applications. Commonly used elements in nanoparticles include gold, silver, copper, zinc, nickel, titanium, magnesium, aluminum, silicon, iron, and yttrium. Nanocrystals may be strategically advantageous as an active antibacterial group because their surface area is exceedingly large relative to their size [1]. The general idea is to use the molecular recognition capability of biomolecules to facilitate the arrangement of nanoscale building blocks in a parallel process, rather than having to assemble these blocks sequentially or individually. For example, nanocrystals can be used as antimicrobials. Nanocrystals are crystalline clusters of a few hundred to a few thousand atoms with the size of a few nanometers. Although, nanocrytals are more complex than individual atoms, their properties are different from those of bulk crystals [3].

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19. Crystalline nanomaterials for antimicrobial applications

Cellulose nanocrystals (CNCs) are a bio-based nanomaterial attracting increasing interest for a range of potential applications. Metal nanocrystals have also been used as an antimicrobial since the 1800. Many pharma companies use nanocrystals to develop medicines or in packaging for medicines. Nucryst Pharmaceuticals (Wakefield, MA) has developed a way to produce metal nanoparticles that can be used as antimicrobiological coatings for medical use [2e6]. The purpose of this chapter is to highlight the use of nanocrystals as antimicrobials. We focus on the role of various metallic nanoparticles as potential antimicrobials and the possible mechanism of their inhibitory actions. The increasing application of nanocrystals as antimicrobials in the industries of medicine, cosmetics, textiles, and food packaging requires an assessment of the toxicity and risks associated with these particles [2].

2. Nanocrystals A nanocrystal is a material particle with at least one dimension smaller than 100 nm based on quantum dots (nanoparticles) and composed of atoms in either a single or polycrystalline arrangement. The size of nanocrystals distinguishes them from larger crystals. They have an advantage for drug delivery systems, as these can increase the solubility of drug several fold. This is fast-growing, industrially feasible technology and is successful in the pharmaceutical and cosmetic industries. The syntheses of nanocrystals requires a highly reliable and simple method to ensure monodispersity and stability. Well-known methods employed, especially those claimed to be one-pot methods, were conducted in Teflon-lined autoclaves. Another widely used method of semiconductor nanocrystals synthesis involves growth from molecular and molten metal droplets. In nanoscience, the dimension of matter is important; typically, it is 0.2e100 nm because the percentage of atoms at the surface of a material becomes more significant [7]. Bulk materials possess relatively constant physical properties regardless of their size, which is not observed at the nanoscale. As the material becomes smaller, the percentage of atoms at the surface increases relative to the total number of atoms of the bulk material. This leads to different properties of nanoparticles, which are partly the result of the surface of the material dominating over the bulk properties. At this scale, the surface-to-volume ratio of materials become large and the electronic energy states become discrete, leading to unique electronic, optical, magnetic, and mechanical properties of the nanomaterial. In general, as the size of organic and inorganic materials decreases toward the nanoscale, their optical and electronic properties vary from the bulk material at the atomic or molecular level and are size- and shape-dependent. The various size-dependent properties that can be observed are quantum confinement in surface plasmon resonance in noble metal particles, superparamagnetic in magnetic materials, and semiconductor particles. Thus, the crystallographic surface and the large surfaceto-volume ratio give nanoparticles prominent properties [8]. The types of nanocrystals are shown in Fig. 19.1.

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3. Types of nanocrystals

TYPES OF NANOCRYSTALS

CELLULOSE NANOCRYSTAL

SILVER NANOCRYSTAL

METAL NANOCRYSTAL

MAGNESIUM OXIDE NANOCRYSTAL

GOLD NANOCRYSTAL

FIGURE 19.1

ALUMINUM OXIDE NANOCRYSTAL

COPPER OXIDE NANOCRYSTAL

ZINC OXIDE NANOCRYSTAL

TITANIUM DIOXIDE NANOCRYSTAL

Types of nanocrystals.

3. Types of nanocrystals 3.1 Cellulose nanocrystals (CNCs) Cellulose is ideal candidate among natural polymers for making nanocrystals due to its strong tensile strength, biocompatibility, cost-effective with high absorption capacity; as well as biodegradability [9]. Furthermore, cellulose in nanocrystalline form has attracted interest because of its increased surface-to-volume ratio, which boosts its binding capacity to other compounds [10,11]. CNCs are crystalline domains extracted from wood fire through acid hydrolysis. They are stiff, rod-like particles with a width of several nanometers and a length of up to hundreds of nanometers [12]. Lower fractions of amorphous regions make them resistant to decay from acid hydrolysis, resulting in large rod structures. CNC is an emerging renewable nanomaterial with promising applications, such as in self-care, food and food products, pharmaceuticals, textiles [13], wastewater treatment [14], solid waste treatment [15], pulp and paper [16], health care [17], and biofuel production [18].

3.2 Metal oxide nanocrystals 3.2.1 Silver nanocrystals Nanocrystals made from silver are known for their electrical conductivity and optical properties as well as for their microbial-resistant nature. Panacek et al. [19] reported colloidal nanocrystals of silver using a modified Tollens process against drug-resistant pathogens. Known implementations of silver nanocrystals are as antimicrobial coatings, wound dressings, and biomedical devices in which silver ions are continuously liberated at a low level to provide protection against bacteria. Silver nanocrystals are incorporated into apparel, plastics, footwear, paint, appliances, keyboards, and textiles for their antibacterial properties. Silver nanocrystals have been examined for their antimicrobial ability against bacteria and have also shown to be active against several types of viruses including human

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19. Crystalline nanomaterials for antimicrobial applications

immunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey poxvirus. Nanocrystals of 25e100 nm were synthesized and used for saccharides had a minimum inhibitory concentration of 6.75e54 mg mL
1(80%), indium-based catalysts have been employed for electrochemical activity for the hydrogenation of CO2 to FA [56,57]. As discussed, bimetallic catalysts are a powerful strategy for enhancing catalytic activity. In2O3eZnO bimetallic nanocrystals were synthesized using the sol-gel method (Fig. 25.7). The composition of the catalyst was tuned, and when with a 5 atm.% In composition, a high faradaic efficiency (95%) was achieved with an FA production rate of 0.4 mmol h1 cm2. Furthermore, DFT confirmed that the ZneIn interface assisted in enhancing the selectivity of FA [47]. 2.1.2 Nanocrystals for asymmetric hydrogenation Asymmetric hydrogenation is an efficient transformation frequently practiced in industry. After realizing the industrial-scale synthesis of L-3,4-dihydroxyphenylalanine (L-DOPA) adopting the enantioselective hydrogenation route, many important fine chemicals including L-menthol and metolachlor (the best-selling chiral herbicide) are manufactured using the enantioselective hydrogenation of C¼O, C¼N, and C¼C functional groups [58]. Most molecules in nature are chiral, such as amino acids, proteins, sugars, and alkaloids. Chirality has a key role in many products such as agrochemicals, pharmaceuticals, flavors, and fragrances. Different methodologies are known for preparing enantiopure compounds. Among them, asymmetric catalysis has a vibrant role (Fig. 25.7). Several factors have to be seriously considered for the design of a suitable catalytic system to achieve a product with high conversion and enantioselectivity [59,60]. Ground-breaking advances in homogeneous catalytic systems employ a metal catalyst and chiral ligand that facilitate suitable stereochemical induction in the product with high enantioselectivities. On the other hand, there have been impressive developments in heterogeneous asymmetric catalysis, and nanocrystals have gained increased attention owing to their tunable size and shape-control properties for potential application in asymmetric transformations.

IX. Conclusion

2. Catalytic applications of nanocrystals

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FIGURE 25.7 (A) High-resolution transmission electron microscopy images and fast fourier transform (FFT) image of 5% In-doped ZnO (Zn0.95In0.05O) nanocrystals; (B) high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image and energy dispersive X-ray (EDX) analysis elemental mapping of In (L shell), Zn (K shell), and O (K shell). Reprinted with permission from I.S. Kwon, T.T. Debela, I.H. Kwak, H.W. Seo, K. Park, D. Kim, S.J. Yoo, J.-G. Kim, J. Park, H.S. Kang, Selective electrochemical reduction of carbon dioxide to formic acid using indiumezinc bimetallic nanocrystals, J. Mater. Chem., 7 (2019) 22879e22883. Copyright 2019 Copyright Clearance Center, Inc.

Despite advances in the field of catalysis, plenty of room is available to contribute creatively to this area. The development of shape-controlled metal nanocrystals is an emerging research area where the effect of the surface structure on catalytic reactions could bridge the gap between existing molecular catalysis and complex supported heterogeneous catalysis. Polyvinylpyrrolidone (PVP)-stabilized Pd nanocrystals with a conclave tetrahedron shape

FIGURE 25.8 Synthetic routes for preparing enantiopure compounds. IX. Conclusion

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25. Metal nanoparticles for catalytic hydrogenation reactions

(Fig. 25.8) were systematically studied to understand residual PVP activity on the enantioselective hydrogenation of acetophenone. PVP adsorbed on Pd concave tetrahedron nanocrystals is detrimental in terms of enantioselectivity. It was reasoned that residual PVP on the surface resists the interaction of acetophenone with the chiral modifier S-proline. This study suggested using KBH4 treatment or hot water reflux to reduce the residual PVP content and increase the prochiral interaction of acetophenone with the chiral modifiers [61]. Early studies observed the remarkable enhancement of selectivity based on the procedure adopted for the reductive environment of supported Pt nanocrystals [62,63]. The treatment of Pt/Al2O3 under a reductive environment was compared with flowing hydrogen at an elevated temperature and other air conditions. The former resulted in almost twice the enantioselectivity compared with the latter. This kind of shift in enantioselectivity was reversible with a change in gas atmosphere and redispersion of the Pt particles, as evidenced by highresolution TEM (HRTEM) [62]. A number of reports exist on the structural sensitivity of hydrogenation using Pt- and Ni-based metals with different chiral modifiers [64,65]. There are also attempts to enhance the enantioselectivity of the hydrogenated product with surface science-based asymmetric catalysis. Differently shaped Pt nanoparticles with a similar size were tested for the enantioselective hydrogenation of a-ketoester and a-ketolactone (Table 25.1 and Scheme 25.1). To study the role of surface morphology in enantioselective transformations, w10-nm nanoparticles with a narrow particle size distribution were chosen for the catalytic study. The Pt nanoparticles were in the fraction of dominantly cubic, cubooctahedral, and octahedral particles (Fig. 25.9). In the absence of a chiral modifier, the hydrogenation reaction TABLE 25.1

Effect of Pt nanoparticle shapes on enantioselective hydrogenation of a-ketoester.

Catalyst

Chiral modifier

Enantioselectivity (%)

Pt-1/SiO2 {100}

CD

72

Pt-2/SiO2 {100} þ {111}

CD

78

Pt-3/SiO2 {111}

CD

86

SCHEME 25.1

Enantioselective hydrogenation using Pt nanoparticles using chiral modifiers.

IX. Conclusion

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477

FIGURE 25.9 (A) Transmission electron microscopy (TEM) image of as-prepared polyvinylpyrrolidone-stabilized Pd concave tetrahedra. (B) Selected area electron diffraction (SAED) pattern of an individual concave tetrahedron. (C) High-resolution TEM (HRTEM) image of an individual concave tetrahedron. (Inset) Enlarged HRTEM image of squared area indicated in (C). Reprinted with permission from N. Su, X. Gao, X. Chen, B. Yue, H. He, The enantioselective hydrogenation of acetophenone over Pd concave tetrahedron nanocrystals affected by the residual adsorbed capping agent polyvinylpyrrolidone (PVP), J. Catal., 367 (2018) 244e251. Copyright 2021 Elsevier.

was independent of the shape of nanoparticles, whereas the addition of chiral modifiers such as cinchonidine or quinine induced a significant increase in the rate (four to 15 times) with an enantioselectivity of 72%e92%. The study showed that by increasing the Pt{111}/Pt{100}ratio, both the reaction rate and enantioselectivity were increased, and confirmed that the reaction is shape-selective [62]. Thus, by understanding that the catalytic performance of metal catalysts also relies on the morphology and atomic arrangement at different facets, extensive research has been directed toward identifying the preparation of metal nanocrystals. However, to synthesize shape-controlled nanocrystals, capping agents such as PVP and cetyltrimethylammonium bromide have been used to refine the exposed facets of the nanocrystals and inhibit aggregation. As discussed, the capping agents and surfactants tend to retain the surface and retard the catalytic behavior of the synthesized nanocrystals. Thus, instead of using conventional capping agents, chiral modifiers with specific functionalities such as amino or carbonyl groups have as similar tendency to bind onto the metal surface. Chen and He attempted to replace traditional capping agents with chiral modifiers such

IX. Conclusion

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