Clay Minerals: Their Antimicrobial and Antitoxic Applications 3031223268, 9783031223266

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Bhaskar Ghosh Dola Chakraborty

Clay Minerals Their Antimicrobial and Antitoxic Applications

Clay Minerals

Bhaskar Ghosh · Dola Chakraborty

Clay Minerals Their Antimicrobial and Antitoxic Applications

Bhaskar Ghosh University of Calcutta Kolkata, West Bengal, India Department of Geology Jogamaya Devi College Kolkata, West Bengal, India

Dola Chakraborty Department of Geology Durgapur Government College Durgapur, West Bengal, India

ISBN 978-3-031-22326-6 ISBN 978-3-031-22327-3 (eBook) https://doi.org/10.1007/978-3-031-22327-3 Jointly published with Capital Publishing Company The print edition is not for sale in Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan and Sri Lanka. Customers from Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan and Sri Lanka please order the print book from: Capital Publishing Company. © Capital Publishing Company, New Delhi, India 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publishers, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publishers nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publishers remain neutral with regard to jurisdictional claims in published maps and institutional affiliations. Disclaimer: Every effort has been made to contact the copyright holders of the figures and tables which have been reproduced from other sources. Anyone who has not been properly credited is requested to contact the publishers, so that due acknowledgment may be made in subsequent editions. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Bhaskar Ghosh dedicates this work to his parents, Prof. M. K. Ghosh and Mrs. Shipra Ghosh, his aunt, Dr. Mridula Basu, and his departed aunt, Late Prof. Bulbul Mitra, for their continued guidance, support, and encouragement since his student life. Dola Chakraborty dedicates this work to her parents, Mr. Debnarayon Chakraborty and Mrs. Kabita Chakraborty, and her husband, Mr. Abhishek Roy Choudhury, for their unwavering support and encouragement throughout this journey.

Preface

Clay minerals, owing to their distinctive internal structures, compositions and properties, have a wide range of socio-economic applications. This book highlights the antimicrobial and antitoxic attributes of these minerals, and endeavours to present a comprehensive description of the state-of-the-art research on all the applications that are based on these attributes. The therapeutic properties of different types of clays have been known to the human civilisation since time immemorial. The ancient medicine men and the medieval physicians, observing the healing properties of clay, prescribed its topical and oral applications for the treatment of many diseases. Neither the causes of those diseases nor the reasons behind the healing action of clays were known to them, which could have enabled better utilisation of clays in medical treatments. It took several centuries of advancement in sciences and technologies to identify the microbes and toxins that were the root causes of such diseases. The internal structures of minerals were also revealed later, after the discovery of X-ray diffraction techniques. Decades of mineralogical studies helped to correlate the internal structures and compositions of different types of minerals with their physical and chemical properties. This approach laid the foundation for understanding the interactions of the clay minerals with different types of chemicals and microbes. There has been a significant advancement in this field over the last few decades, which facilitated the formulation of more effective therapeutic agents from the clays and their derivative products, and also helped to find more applications of clays in the pharmaceutical industries. However, some aspects of clay-microbe or clay-toxin interactions are yet to be fully understood, and investigations are still going on. We have highlighted here the latest studies in this field that throw light on the interactions of clays with microbes and toxins, and described the therapeutic applications of the clays that are based on the antimicrobial and antitoxic properties. Such a discourse is expected to introduce the students pursuing undergraduate and post-graduate studies in chemistry, physics and geology with some important socio-economic applications of the concepts they learn and encourage them to carry out research work in related fields in the future. Furthermore, the pharmacologists, biochemists, and all the scientists engaged in medicinal research are looking for new ingredients for medicines, which will enable them to vii

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meet the challenges of newly introduced strains of different types of microbes and antibiotic-resistant bacteria. They can explore the vast potentialities of clay for a feasible solution because it is readily available, less expensive, more versatile and has fewer side effects than most other medicinal ingredients. This book will provide such researchers with all the theoretical knowledge they need to initiate their investigations in this field, from the most preliminary concepts of mineralogy, chemistry, and physics that are useful in this context, to the detailed reviews of the extensive research works done so far. As required by the objectives of this book, it was essential to give comprehensive explanations on selected topics of mineralogy, physics, chemistry, and microbiology. Discussing such a wide variety of topics within two covers was not an easy task. It was even more difficult to make the explanations as simple as possible so that the concepts can be grasped easily by readers with diverse academic backgrounds, such as physics, chemistry, geology, and biological sciences. Considering the difficulties a reader may face while trying to grasp the new concepts of another subject area, we have made the discussions very simple that can be easily understood by all. Even the most preliminary concepts have been explained elaborately, with suitable examples and schematic diagrams, so that even the readers with high school level knowledge of science would not have any problem understanding them. In addition, 168 thoughtprovoking questions over different conceptual aspects are given at the end of the book to encourage the thinking process, which will definitely help to understand the subjects more clearly. A systematic and sequential approach has been followed in this book, which will also help to develop the new concepts properly. The discussion starts with some important mineralogical, physical and chemical aspects of clays, followed by their interactions with microbes and toxins, and then their applications in the treatment of diseases caused by pathogens and toxins. For this purpose, the book is organized into seven chapters, as described below. Chapter 1 introduces the terms clays and clay minerals to the readers and gives short but comprehensive explanations on the composition, classification, and internal structures of the clay minerals. The physical and chemical properties of clay minerals that are related to their antimicrobial and antitoxic actions are also explained in this chapter. Chapter 2 explains the mechanisms of the antimicrobial and antitoxic actions of clays, providing detailed descriptions of the latest researches that help to understand these mechanisms. The internal structures, compositions and properties of the clay minerals have also been correlated with their interactions with microbes and toxins. The first two chapters, thus, lay the foundation for discussing the applications of clay minerals given in the next four chapters. Chapter 3 describes some instances of the traditional applications of clays in the treatment of diseases caused by microbes. Present-day applications of the clay minerals for protecting human health from microbes and toxins are described in Chaps. 4 and 5 respectively. Chapter 6 gives an overview of the prospective applications of clays for the prevention and cure of COVID-19.

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The concluding chapter (Chap. 7) explores the scope for the production of more effective and more versatile medicines from clay minerals in the future and discusses the potentialities of nanoclays and various clay derivatives in this context. The advantages of clay minerals over the other medicine ingredients and a few detrimental effects of the clay-based industries on the environment have also been explained in this chapter. The students of chemistry, physics, and geology may not be familiar with the medical terms used in Chaps. 4 and 5. The definitions and brief explanations of such terms are given at the end of these two chapters for their convenience. In order to avoid any possible confusion, it is required to specify the intended meanings of some of the terms used by us. The term ‘antimicrobial action’ in this book refers to the protective actions of clays against all types of pathogens, including viruses, bacteria, fungi, protozoa etc. Such usage may not agree with the definitions of microbes given in some common dictionaries and encyclopedias (e.g. Merriam-Webster Dictionary, 20221 ), where bacteria, protozoa, fungi, algae, amoeba and molds are considered microbes, excluding the viruses. A commonly used definition of a microbe is: “a very small living thing, especially one that causes disease, that can only be seen with a microscope” (Cambridge Dictionary, 20222 ). The viruses, due to their dual existences, act as living beings inside a host cell and behave as nonliving objects outside it. They can be justifiably considered as microbes in the former case, which we have preferred to use in this book. Similar use of the term ‘microbe’ has also been suggested by the National Center for Biotechnology Information of Germany3 and the American Society for Microbiology of the USA.4 The term toxin is commonly defined in the medical literature as “a poisonous protein produced by pathogenic bacteria, various animals, notably venomous snakes or certain plants” (after the American Medical Association Encyclopaedia of Medicine5 ). However, the clay minerals can protect us from a wide range of harmful organic and inorganic substances, including many hazardous industrial wastes, heavy metals, agricultural chemicals (such as fertilizers, pesticides and herbicides), and the poisonous proteins that are synthesised by bacteria, fungi and other parasites outside or inside the human body. In this book, all these detrimental substances coming from varied sources have been referred to as ‘toxins’, and the antitoxic applications described here include the protective actions of the clay minerals against all of them. 1

Definition of “Microorganism” from the Merriam-Webster.com Dictionary. Merriam-Webster. (Accessed 14th June, 2022). https://www.merriam-webster.com/dictionary/microorganism. 2 Definition of “Microbe” from the Cambridge Academic Content Dictionary. Cambridge University Press. (Accessed 14th June, 2022). https://dictionary.cambridge.org/dictionary/english/microbe. 3 National Center for Biotechnology Information (2019). What are microbes? Institute for Quality and Efficiency in Health Care, National Center for Biotechnology Information, Cologne, Germany. (Accessed 14th June, 2022). https://www.ncbi.nlm.nih.gov/books/NBK279387/#_NBK279387_ pubdet. 4 Hariharan, J. (2021). What counts as a Microbe? American Society for Microbiology. https://asm. org/Articles/2021/April/What-Counts-as-a-Microbe. 5 Clayman, C. B. (1989). American Medical Association Encyclopaedia of Medicine. Dorling Kindersley Limitedand the American Medical Association.

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Here also, the context of this book necessitated using a more generalised definition of ‘toxin’, deviating from its commonly used definition. It is important to note that the discussions featured in this book are limited to the therapeutic applications of the clay minerals that are based on their antimicrobial and antitoxic properties. The same properties of these minerals can also be utilised to purify the water and soil from pathogens and harmful substances. But these aspects are not included in this book, since a comprehensive discussion on the applications of clays in the diverse fields of waste management and environmental protection requires writing another book of similar size. We have a plan to write a separate book in future to address these matters properly. It is also worth mentioning that conforming to the title of this book, we have not discussed here the therapeutic applications of clays that are not related to their antimicrobial and antitoxic actions, like geophagy, skin nourishment, etc. Finally, we would like to state that, we will be immensely grateful to the readers if they mail us their valued suggestions for the betterment of this book. If the students face any difficulty understanding any of the concepts presented here, they are most welcome to communicate with us by e-mail. We will be glad to help them out. Kolkata, India Durgapur, India July 2022

Bhaskar Ghosh Dola Chakraborty

Acknowledgements

This book is the result of the inspirations and guidance we have obtained from the immense volume of research works carried out so far on different specialised topics of mineralogy, chemistry, physics, microbiology, toxicology and pharmacology. All these works have been cited in the relevant parts of this book, and their detailed references are given in the ‘References and Further Reading’ section at the end of each chapter. With due respect, we gratefully acknowledge the invaluable contribution of a large number of researchers throughout the world who have performed these studies. It would be a fitting tribute to them if we are successful in conveying the knowledge obtained from their enormous works to the present day students and future researchers. We express our deep appreciation to Dr. Amilan Jose, Assistant Professor of Department of Chemistry, National Institute of Technology, Kurukshetra, Haryana for reviewing the first chapter of this book. His valuable comments and suggestions helped us to improve this chapter significantly. Our sincere thanks to Dr. Swapna Mukherjee, former Senior Director of Geological Survey of India, for her encouragement in the initial stage of our work. We take this opportunity to express our homage and gratitude to all the teachers who have helped us to grasp the basic ideas of mineralogy, chemistry, physics and biological sciences in our student days. We have tried our best to provide simple, easily understandable explanations for all the scientific concepts introduced in this book, so that a beginner has no difficulty to develop the basic ideas. If we are successful in this respect, then the credit goes to our young, inquisitive students; many years of interactions with them have helped us to identify the problems they face while learning a new subject, and the concepts they find difficult to understand. Finally, we gratefully acknowledge the support and cooperation provided by Capital Publishing Company, New Delhi in the final stage of our work.

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About This Book

This work attempts to provide a comprehensive description of the antimicrobial and antitoxic actions of clay minerals, which facilitate their applications as disinfectants and medicines ingredients. While the presently available literatures highlight only a few aspects of medicinal clays, a comprehensive text on all their major therapeutic applications is lacking. This book endeavours to fill up this lacuna. It further elucidates the properties of clay minerals that facilitate their antimicrobial and antitoxic actions, and how these properties are related to the chemical compositions and internal structures of the mineral groups. More than 150 thought-provoking questions at the end will give the readers a better insight of this subject. The simple, easily comprehensible definitions and explanations of all the relevant scientific terms provided in this book will help the beginners to develop a clear understanding, and remove any confusion resulting from the ambiguous usage of these terms in the existing literature.

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Contents

1 An Overview of the Clay Minerals: Composition, Classification, Internal Structure and Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Clay Minerals and Clays: What They Actually Are . . . . . . . . . . . . . . 1.2 Composition and Classification of the Clay Minerals . . . . . . . . . . . . 1.3 Internal Structures of the Clay Minerals . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Specific Surface Area of the Clay Minerals . . . . . . . . . . . . . . . . . . . . . 1.5 Colour of Clay Minerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.6 Cation Substitution and Cation Exchange Capacity (CEC) of Clay Minerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.7 Clay Mineral as Adsorbents of Organic and Inorganic Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Clay-Induced Antimicrobial and Antitoxic Mechanisms: How Do the Clays Protect Us from Pathogens and Toxins? . . . . . . . . . . . . . . 2.1 Clays Protecting from Viral Infections: The Mechanism of Virus Adoption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1 The Role of Cations in the Adsorption Mechanism . . . . . . . . 2.1.2 Flocculation and the Virus Adsorption Mechanism . . . . . . . . 2.1.3 The Importance of CEC of Clays in Virus Adsorption . . . . . 2.1.4 Effects of Van der Waals Forces of Attraction and Hydrogen Bonding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.5 Effects of Specific Surface Area and Surface Charge Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.6 Possible Effects of Other Physico-Chemical Properties of Clays on Their Virus Adsorption Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.7 Effects of Presence of Organic Matters . . . . . . . . . . . . . . . . . . 2.1.8 Strength of Bonding Between the Clay Surfaces and the Adsorbed Viruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 1 3 6 13 15 17 20 22 25 25 27 27 29 31 31

32 33 33

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2.2 Antibacterial Actions of Clay Minerals . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 The Mechanisms of Clay-Supported Bactericidal Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2 Adsorption of Bacteria on Clay Surfaces . . . . . . . . . . . . . . . . 2.2.3 Other Antibacterial Actions of Clays . . . . . . . . . . . . . . . . . . . . 2.3 Loading of Clay Interlayer Spaces with Antimicrobial Cations . . . . 2.4 Antitoxic Actions of Clays: Mechanism and Controlling Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Traditional Applications of the Antimicrobial and Antitoxic Properties of Clay Minerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Clays in the Healing of Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 The Traditional Ways of Killing Bacteria with Clays . . . . . . . . . . . . . 3.3 Peloid Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Antimicrobial Applications of Clays and Their Derivatives in Protection of Human Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Application of Antimicrobial Property of Clay Minerals in the Treatment of Common Diseases . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Other Application of Clay Minerals in Medicines . . . . . . . . . . . . . . . 4.3 Interactions of Clay Minerals with Gastrointestinal Mucus . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Antitoxic Applications of Clays in the Protection of Human Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Quantitative Representation of Adsorption Potential: The Sorption Coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Clay Minerals in the Treatment of Orally Ingested Toxic Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Clay Minerals in the Treatment of Toxic Substances Synthesised Within Human Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34 35 39 41 43 43 48 55 56 57 58 59 61 63 66 67 75 79 80 82 83 87

6 Clays in the Global War Against COVID-19: Why are They Preferable Over the Conventional Weaponry? . . . . . . . . . . . . . . . . . . . . 91 6.1 Characteristic Features of SARS-CoV-2 . . . . . . . . . . . . . . . . . . . . . . . 92 6.1.1 Common Variants of SARS-CoV-2 . . . . . . . . . . . . . . . . . . . . . 94 6.1.2 Entry of SARS-CoV-2 in Human Cells: The Role of hACE2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 6.1.3 Effects of SARS-CoV-2 on Human Health . . . . . . . . . . . . . . . 97 6.2 Prevention of Covid-19: Common Practices and Associated Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 6.2.1 Effects of Soaps on Human Skin . . . . . . . . . . . . . . . . . . . . . . . 100 6.2.2 Effects of Alcohol-based Sanitisers and Surface Sprays on Human Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

Contents

6.2.3 Effects of Detergents on Human Health and Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3 Clays in Covid-19 Prevention: Disinfectants that Are Safe for Human Health and Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.1 Clay-based Hand Sanitisers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.2 Clay-based Surface Disinfectants . . . . . . . . . . . . . . . . . . . . . . . 6.3.3 Clay Preventing Airborne Virus Propagation . . . . . . . . . . . . . 6.3.4 Clay Against Virus Propagation from Biomedical Wastes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4 Prospective Application of Clays in the Treatment of COVID-19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4.1 Clays in the Treatment of Similar Viruses . . . . . . . . . . . . . . . . 6.4.2 Prospects of Developing Drugs from Nano-Clays for Healing SARS-CoV-2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4.3 Clay in the Drug Delivery Systems of Anti-COVID-19 Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4.4 The Expected Synergistic Actions of Clay-based Drugs: Double-Edged Swords Against COVID-19? . . . . . . . References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 The Present and the Future: Advantages, Drawbacks, and Future Prospects of Clays for Protection of Human Health . . . . . 7.1 Advantages of Clay Minerals Over the Other Medicine Ingredients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.1 Therapeutic Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.2 Economic Consideration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.3 Health and Environmental Considerations . . . . . . . . . . . . . . . 7.1.4 Better Alternative for Preventing the Spread of Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Antimicrobial Applications of Clay Nanocomposites and Clay-Drug Nanohybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 The Multifaceted Applications of Nanotechnology in Medical Sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.2 Properties of Nanomaterials Favourable for Their Medical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.3 Basic Ideas on Clay Nanocomposites and Nanohybrids . . . . 7.2.4 Nanoclay Derivatives in Pharmaceutical Industries . . . . . . . . 7.2.5 Nanoclay Derivatives in Food Preservation and Packaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Potential Environmental Hazards of Clay-based Medicinal Industries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4 Suggested Fields for Future Investigations . . . . . . . . . . . . . . . . . . . . . 7.4.1 Mineralogical and Material Scientific Researches . . . . . . . . . 7.4.2 Pathogenic and Microbiological Investigations . . . . . . . . . . .

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103 105 105 108 109 109 110 110 111 113 115 116 123 124 124 125 125 127 127 128 129 130 131 133 134 136 137 138

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7.4.3 Chemical and Biochemical Investigations . . . . . . . . . . . . . . . . 139 7.4.4 Researches on Nanoclays and Nanoclay Derivatives . . . . . . . 140 References and Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Think for a While . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Index of Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

About the Authors

Dr. Bhaskar Ghosh has been teaching mineralogy, structural geology and some topics of applied geology in Jogamaya Devi College for more than twenty years. He has also worked as a guest lecturer and/or examiner in different undergraduate and post-graduate institutions of West Bengal. He has carried out doctoral research on the deformational structures and stratigraphy of the Precambrian rock successions of Singhbhum Craton, Eastern India. His interest also include the study of different aspects of mineralogy and clay sciences, especially the interrelationship of the internal structures, compositions, properties and socio-economic applications of the clay minerals and other types of silicates. Dr. Dola Chakraborty is an Assistant Professor of Geology in Durgapur Government College. Her doctoral research were in the geomorphology and sediment character of beach-dune complex along different sectors of north-eastern coast of India. Her research on heavy mineral studies and the science of clays have been published in various journals and presented at different conferences in recent years.

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Chapter 1

An Overview of the Clay Minerals: Composition, Classification, Internal Structure and Properties

Introduction This book portrays a comprehensive discussion on the antimicrobial and antitoxic applications of the clay minerals and their synthetic derivatives, and the related physical, chemical and biological processes that are involved in the destruction or removal of the pathogens and the toxins. For a better perception of all these applications and associated processes, the readers from different disciplines and academic backgrounds may require some preliminary knowledge of the mineralogical, physical and chemical aspects of the clays. This chapter lays the foundation for the entire discussion, by presenting simple, easily comprehensible explanations on the compositions, classification, and internal structures of the clay minerals. It also gives an overview of the physical and chemical properties of these minerals that are important in their antimicrobial and antitoxic applications.

1.1 Clay Minerals and Clays: What They Actually Are The term clay minerals refer to a number of mineral species belonging to the phyllosilicate subclass of the silicate class. Like all the other minerals, the clay minerals are natural, inorganic, homogeneous solids. Each of them has a definite (but not necessarily fixed) chemical composition, and a fixed ordered internal structure. The ordered array of atoms or ions in a clay mineral is manifested in its crystalline structure, which can be detected by its distinctive X-Ray diffraction pattern. These mineral species, along with some other minerals (associated minerals) and some non-mineral matters (associated phases), are the essential constituents of clays (see the chart given in Fig. 1.1). A brief description of clay and its constituent matters are given below. The universally accepted definition of clay, given by the Joint Nomenclature Committee (JNC), constituted from the Association International epourI’ Etuddes Argiles (AIPEA) and Clay Minerals Society (CMS), is as follows: © Capital Publishing Company, New Delhi, India 2023 B. Ghosh and D. Chakraborty, Clay Minerals, https://doi.org/10.1007/978-3-031-22327-3_1

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1 An Overview of the Clay Minerals: Composition, Classification …

Fig. 1.1 The constituents of clays: the clay minerals, associated minerals and associated phases

The term “clay” refers to a naturally occurring material composed primarily of fine-grained minerals, which generally becomes like plastic when appropriate water contents are added and will harden when dried or put on fire (Guggenheim and Martin 1995, 1996). The materials that fulfill the conditions stated in this definition are kaolin, China clay, bentonite, bleaching earth, common clay, ball clay, fire clay and refractory clay. A detailed discussion on the definition of clay is given by Ghosh (2013). Clay minerals: The following definition given by Guggenheim and Martin (1995) has been recommended by the JNC: The term “clay mineral” refers to a number of phyllosilicate minerals, which impart plasticity to clays, and which harden upon drying or firing. Ghosh (2013) provided a comprehensive explanation of the above definition, along with a critical review of its different aspects. The clay minerals, owing to their unique internal structure, are capable of incorporating water molecules in their inter-layer spaces. These water molecules are removed when the clay minerals are heated or desiccated. The clay minerals are, therefore, responsible for the characteristic properties of the clays in which they are present, and in this respect, they differ from the other constituents of clay. Associated minerals: These mineral constituents of clay include the phyllosilicates like talc, pyrophyllite, chlorites, muscovite, etc., tectosilicates like quartz and feldspars, and many of them belong to the oxide and hydroxide classes (e.g., corundum, gibbside, boehmite, diaspore, magnetite, hematite, goethite, lepidocrocite, etc.). All these minerals, even the phyllosilicates, are not plastic when wet and do not harden by drying or firing. Thus unlike a clay mineral, the associated minerals are not responsible for the characteristic properties of the clays in which they are present, and are therefore included in a separate category of clay constituents.

1.2 Composition and Classification of the Clay Minerals

3

Associated phases: Clay minerals and associated minerals are essentially inorganic and crystalline. But some common constituents of clay are amorphous (e.g., allophone, imogolite, etc.) or organic materials (e.g., peat, humus, etc.) or both. These non-mineral phases are included in the third category of clay constituents, known as the associated phases.

1.2 Composition and Classification of the Clay Minerals (i) Hierarchical position of clay minerals in the mineral world: The minerals are essentially natural, inorganic solids. The mineral world is divided into eight major mineral classes by Danain (1848), based on the dominant anions or anionic groups present in them (Dana and Ford 1915). Each class is further categorised into a number of subclasses, which are in turn divided into some groups, based on their structural and compositional affinities. Each mineral group contains a number of mineral species, and each mineral species is characterised by a fixed internal structure and a definite chemical composition. In many cases, the chemical compositions of all mineral species belonging to a group may be represented by a general chemical formula. The clay minerals belong to the phyllosilicate subclass in the silicate class. They are categorised into six groups based on their compositions and structures: kaolinite, illite, smectite, vermiculite, palygorskite-sepiolite and mixed layer clays. (ii) General chemical composition of clay minerals: All the silicate minerals, including the clay minerals, consist of the anionic group [SiO4 ]4– .. In this anionic group, one Si4+ is surrounded by four O2– (Fig. 1.2), forming the 4-fold or tetrahedral coordination polyhedron known as [SiO4 ]4– tetrahedron. The excess negative charge of the [SiO4 ]4– tetrahedral is balanced by cations in octahedral coordination sites. In some silicate minerals, there may be limited substitution of Si4+ by Al3+ in the tetrahedral site, and the excess negative charge is balanced by the incorporation of monovalent (Na+ , K+ ) or bivalent (Ca2+ ) cations in a 12-fold coordination site. Like all the minerals of the phyllosilicate subclass, the ratio of tetrahedral cations (Si4+ and Al3+ ) and oxygen in the clay minerals is 2:5 or 8:20. In the kaolinite group, there is no substitution of Si4+ by Al3+ in the tetrahedral sites, while this substitution is common in the other groups, along with consequent inclusion of monovalent or bivalent cations in the 12-fold coordination sites. Based on the above discussion, the general chemical composition of all the clay mineral groups can be expressed with the following structural formula. One formula unit comprises eight [SiO4 ]4– tetrahedra. Xn Y4−6 (Si8−n Aln ) O20 (OH)4 · mH2 O

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1 An Overview of the Clay Minerals: Composition, Classification …

Fig. 1.2 The SiO4 4− tetrahedron, constructed by joining the centres of four O2− (Grey spheres). The Si4+ (brown sphere) is situated at the centre of the tetrahedron. Since the ionic radius of Si4+ is one-fifth of that of O2− ,it is behind the O2− and not visible from the outside. a Side view of an SiO4 4− tetrahedron. Its outline appears as a quadrilateral in this view. b Apical view of an SiO4 4− tetrahedron, which is the plan view with one apical O2− pointing towards the observer. Its outline appears as a triangle in this view

X Y N

K, Na or Ca at12-fold coordination sites. Al, Mg, or Fe at octahedral coordination sites. number of Si4+ substituted by Al3+ in each formula unit of eight tetrahedral coordination sites. n = 0 in the clay mineral species with no substitution of Si4+ by Al3+ at the tetrahedral site. m number of H2 O molecules in each formula unit of eight tetrahedral coordination sites. In some clay mineral species, there is no H2 O molecule; i.e., m = 0.

The geometric array of the above three types of cationic sites is described in the next Sect. 1.3. The chemical compositions of some common clay mineral species, which have been referred to in the other chapters of this book, are given below. (iii) Composition of kaolinites: The mineral species belonging to the kaolinite group are: kaolinite, halloysite, dickite, nacrite, lizardite, berthierine, amesite, cronstedtite, nepouite, kellyite, fraipontite, brindleyite. Kaolinite is the most common mineral species in this group, after which the group has been named. In the case of kaolinite, n = 0, and Y = Al, and thus the chemical formula is: Al8 Si8 O20 (OH)16 Another common species of this group, halloysite, contains a variable amount of water of crystallisation (.H2 O), which may be removed on heating. In a dehydrated state, it has the same chemical composition as kaolinite, although its internal

1.2 Composition and Classification of the Clay Minerals

5

structures are different. The general chemical formula of halloysite is given below: Al8 Si8 O20 (OH)16 .nH2 O where n is commonly 2, though it can be >2 in some cases. (iv) Composition of illites: The illite group comprises the species illite, glauconite, brammallite, wonesite, etc. This group has been named after illite, which is the most common mineral species belonging to this group. The formula of the species illite is: Kn Al4 [(Si8−x , Alx ) O20 ] (OH)4 , where x is always < 3 and commonly 1 < x < 1.5. (v) Composition of smectites: The smectite group comprises montmorillonite, beidellite, nontronite, volkonskoite, saponite, hectorite, sauconite, stevensite, swinefordite, etc. The most common mineral species of this group is montmorillonite, which has the following composition: (1/2Ca, Na)(Al, Mg, Fe)4 [(Si, Al)8 O20 ](OH)4 .nH2 O (vi) Composition of Vermiculites: The vermiculite group, consisting of dioctahedral and trioctahedral vermiculite species, has the following general chemical formula: ) ( (Mg, Ca, Na)0.6−0.9 Mg, Fe3+ , Al 6 [(Si, Al)8 O20 ](OH)4 . mH2 O (vii) Composition of palygorskite and sepiolite: The mineral species palygorskite, sepiolite, loughlinite, falcondoite, and yofortierite are included in the palygorskite-sepiolite group. The compositions of palygorskite and sepiolite, the two most common minerals of this group, are given below. Palygorskite: (Mg, Al)4 Si8 O20 (OH)2 ·8H2 O. Sepiolite: Mg5.3 Si8 O20 (OH)2 ·8H2 O. (viii) Composition of mixed-layer clays: In the group of mixed-layer (Interstratified) clay minerals, the species included are brinrobertsite, kulkeite, aliettite, rectorite, hydrobiotite, corrensite and tosudite. The chemical composition of the species brinrobertsite is given below.

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1 An Overview of the Clay Minerals: Composition, Classification …

(Na,K,Ca)n (Al,Fe,Mg)4 (Si,Al)8 O20 (OH)4 m(H2 O) [n = 0.35, m = 3.54] The chemical composition of the species kulkeite is: Na0.35 Mg8 AlSi7 O20 (OH)10 . Compositions of some common types of clays are given below. Bentonite is a common type of clay (not clay mineral) with a wide range of antimicrobial and antitoxin applications. This clay is predominantly composed of the clay mineral montmorillonite. Montmorillonites commonly contain Ca2+ or Na+ in their interlayer cationic positions (see Sect. 1.3). Based on the cation present in montmorillonite, bentonite is classified into calcium bentonites and sodium bentonites, composed of Ca2+ -rich montmorillonite and Na+ -rich montmorillonite, respectively. Another rare type, potash (or potassium) bentonite, is composed mainly of K+ rich illites that are alteration products of montmorillonite.

1.3 Internal Structures of the Clay Minerals As defined in Sect. 1.1, the clay minerals, essentially belong to the phyllosilicate subclass of the silicate class. The fundamental structural unit of all the silicate minerals is the [SiO4 ]4– tetrahedron, comprising four apical O2– and a central Si4+ . Different views of this tetrahedron are shown in Fig. 1.2, which is obtained by joining the centres of the four O2– with four imaginary lines. The Si4+ ion at the centre, being much smaller than the apical anions, is not visible from outside. Its position in the tetrahedron is marked with a sphere with a dashed outline. In the phyllosilicate subclass, each tetrahedron is linked to its three neighbouring tetrahedral by sharing three apical O2– , thus forming a continuous layer or sheet of [SiO4 ]4– tetrahedral (Figs. 1.3 and 1.4), known as the t-layer. Each tetrahedron in the t-layer thus comprises three bridging O2– , which connect it to three other tetrahedra; and one non-bridging oxygen, which is not shared with another tetrahedron. All the non-bridging O2– are on the same side of the t-layer of a phyllosilicate mineral, thus forming a continuous atomic plane of non-bridging O2– in the t-layer. Figure 1.3 shows the plan view of a tetrahedral layer from the apical side, in which all the non-bridging O2– of the connected [SiO4 ]4– tetrahedra point towards the viewer. Figure 1.4, on the other hand, shows the same tetrahedral layer from the basal side, with all the non-bridging O2– pointing away from the viewer. In many phyllosilicates, the atomic plane of non-bridging O2– contains hydroxyl groups or OH– (Fig. 1.5). On that plane, each OH– is surrounded by six non-bridging O2– in a hexagonal array. In Fig. 1.5, the atomic plane containing non-bridging O2– and OH– is marked by blue, and the hexagonal array of the O2– around the central OH– is marked by blue dashed lines.

1.3 Internal Structures of the Clay Minerals Fig. 1.3 The plan view of a continuous tetrahedral layer (t-layer) of a phyllosilicate mineral, from the apical side. The non-bridging O2− (white sphere) of each SiO4 4− tetrahedron points towards the observer. The three bridging O2− (grey sphere) of each SiO4 4− tetrahedron are shared by three adjacent tetrahedra. The Si4+ at the centre of each tetrahedron is behind the non-bridging O2− , therefore not visible in this view. N.B. The spheres represent the positions of different ions in the structural framework, not their relative sizes

Fig. 1.4 The plan view of a continuous tetrahedral layer (t-layer) of a phyllosilicate mineral, from the basal side. The non-bridging O2− of each SiO4 4− tetrahedron points away from the observer, and is not visible in this view. The three bridging O2− (grey sphere) of each SiO4 4− tetrahedron are shared by three adjacent tetrahedra. The Si4+ is at the centre of each tetrahedron. N.B. The spheres represent the positions of different ions in the structural framework, not their relative sizes. Though Si4+ and O2− are represented by the spheres of same size, the former is much smaller

7

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1 An Overview of the Clay Minerals: Composition, Classification …

Fig. 1.5 Position of the OH– in the atomic plane of non-bridging O2− inclay minerals and other phyllosilicates

The non-bridging O2– and hydroxyl groups in the t-layer are coordinated with bivalent or trivalent cations in octahedral coordination sites. Those cation-centred octahedral may be linked together by sharing their apical anions, to form a continuous layer of octahedral or o-layer parallel to and connected with the t-layer. If the octahedral cations in the o-layer are bivalent like Mg2+ , Fe2+ etc., then each apical anion of the octahedron is surrounded by three cations, and the phyllosilicates are called tri-octahedral (Figs. 1.6, 1.7 and 1.8). In contrast, the non-bridging O2– and hydroxyl groups in the di-octahedral phyllosilicates (Fig. 1.9) are coordinated with trivalent octahedral cations such as Al3+ , with each apical anion in the octahedron surrounded by two cations. In the tri-octahedral phyllosilicates, all the octahedral in the o-layer are occupied by bivalent cations, while two-third of octahedral in the di-octahedral phyllosilicates are occupied by trivalent cations, and the remaining one-third are vacant. A few groups of phyllosilicate have a structural unit comprising one t-layer and one o-layer that are parallel to each other, forming an electrically neutral t–o layer (Fig. 1.6). The crystal structure of these phyllosilicates has a continuous stacking of t–o layers, which are bonded together by weak Van der Waals force. The clay minerals of the kaolinite group and some other phyllosilicates show this type of structure. Some phyllosilicate groups have a structural unit known as the t–o–t layer (Fig. 1.7), comprising two parallel t-layers and one o-layer in between them. The two t-layers in these minerals are arranged in such a way that their atomic planes of non-bridging O2– and the hydroxyl groups face each other, and are connected to

1.3 Internal Structures of the Clay Minerals

9

Fig. 1.6 A structural cross section perpendicular to the tetrahedral sheets of a phyllosilicate mineral with the tri-octahedral t–o structure, showing the stacking of tetrahedral and octahedral layers (tlayer and o-layer, respectively) and the positions of different cations and anions. All the octahedral sites in the o-layers are filled up by bivalent cations. N.B. The spheres represent the positions of different ions only, not their relative sizes

the middle o-layer. The t–o–t layers are electrically neutral and bonded together by weak Van der Waals force. The phyllosilicates like talc (trioctahedral), pyrophyllite (di-octahedral), etc. show this type of structure. In some phyllosilicates with t–o–t layers, however, a number of tetrahedral Si4+ sites are substituted by Al3+ , resulting in a charge imbalance. The excess negative charge is balanced by the inclusion of monovalent or bivalent cations in the interlayer space, i.e., in between two t–o–t layers, thus forming a t–o–t–c structure where c represents the interlayer cations (Figs. 1.8 and 1.9). This structure is found in many clay minerals belonging to illite, smectite, and vermiculite groups, and also in most of the common micas such as muscovite (di-octahedral), biotite (tri-octahedral), paragonite, phlogopite, lepidolite, etc. The minerals of the phyllosilicate subclass are further categorised into a number of mineral groups, based on their structural and compositional similarities. A detailed

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Fig. 1.7 A structural cross section perpendicular to the tetrahedral sheets of a phyllosilicate mineral with the tri-octahedral t–o–t structure, showing the stacking of tetrahedral and octahedral layers (tlayer and o-layer, respectively) and the positions of different cations and anions. All the octahedral sites in the o-layers are filled up by bivalent cations. N.B. The spheres represent the positions of different ions only, not their relative sizes

1.3 Internal Structures of the Clay Minerals

11

Fig. 1.8 A structural cross section perpendicular to the tetrahedral sheets of a phyllosilicate mineral with tri-octahedral t–o–t–c structure, showing the stacking of tetrahedral and octahedral layers (tlayer and o-layer respectively) and the interlayer cations. All the octahedral sites in the o-layers are filled up by bivalent cations. N.B. The spheres represent the positions of different ions only, not their relative sizes

discussion on the structural types of phyllosilicates is beyond the scope of this book– the succeeding part presents a brief description of the structures of the five clay mineral groups only. (i)

Kaolinite group: In the minerals of this group, one t-layer is connected to one o-layer, to form an electrically neutral structural unit known as the t–o layer. Since the octahedral spaces are mostly occupied by trivalent Al3+ , the minerals belonging to the kaolinite group generally have di-octahedral t–o structures. In the crystals of kaolinite, one t–o layer is connected with another by weak Van der Waals force. Since this weak bonding between them can be easily broken, these crystals have a very strong tendency to split long parallel planes. For this reason, they commonly occur as very thin flakes or sheets instead of equidimensional grains. (ii) Illite, smectite, and vermiculite groups: The mineral structures of these three groups are composed of tri-octahedral or di-octahedral t–o–t layers. In the osheets, 4 out of 6 apical anions of each octahedron are O2– , and the remaining

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Fig. 1.9 A structural cross section perpendicular to the tetrahedral sheets of a phyllosilicate mineral with the di-octahedral t–o–t–c structure, showing the stacking of tetrahedral and octahedral layers (t-layer and o-layer, respectively) and the interlayer cations. Two-third of the octahedral sites in the o-layer are filled up by trivalent cations, and the remaining one-third are vacant. N.B. The spheres represent the positions of different ions only, not their relative sizes

two are OH– . But in their tetrahedral sites, there is the limited substitution of Si4+ by Al3+ . Their internal structures, therefore, differ from those of the kaolinites. The excess negative charge thus created in each t–o–t layer is balanced by monovalent or bivalent cations, like K+ , Na+ , Ca2+ , Mg2+ etc. In the crystals of illite, smectite, and vermiculite, these cations connect two negatively charged t– o–t layers, occurring in the interlayer space in between them. The clay minerals of these three groups, therefore, have trioctahedral or dioctahedral t–o–t–c structures. Although the inter layer cations in these clays reduce the repulsive force in between the two negatively charged t–o–t layers, the bond between them is very weak. They also occur as very thin flakes like the kaolinites. (iii) Palygorskite—sepiolite group: In the minerals of this group, the cationic octahedral do not form o-layers. These octahedral are linked together in a linear array in the form of chains or ribbons, which are connected to the t-layers. There are many vacant spaces in between the octahedral chains.

1.4 Specific Surface Area of the Clay Minerals

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A few authors (e.g., Kumari and Mohan 2021) have included the minerals of this group in the chain silicate (inosilicate) subclass instead of phyllosilicate, possibly due to the chain-like arrangement of cationic octahedra. But we still prefer to include them in the phyllosilicate subclass for the following two reasons: (a) In the inosilicates, the tetrahedral are arranged in a one-dimensional pattern to form continuous single chains (as in pyroxenes) or double chains (as in amphiboles). But in the minerals of the palygorskite-sepiolite group, the [SiO4 ]−4 tetrahedra are arranged in a two-dimensional pattern, to form the continuous t-layers like all the other phyllosilicates. (b) As shown in Sect. 1.2(vii), the silicon:oxygen ratio in palygorskite and sepiolite is 8:20, i.e., 2:5. This is the characteristic ratio of tetrahedral cation and oxygen in all phyllosilicate. In contrast, this ratio is 1:3 in the single-chain silicates, and 4:11 in the double chain silicates.

1.4 Specific Surface Area of the Clay Minerals The specific surface area of a solid is its total surface area per unit mass, i.e., the ratio of its area and its mass. Its dimension is L2 M–1 and the SI unit is m2 /kg, though the unit m2 /g is commonly used for very fine mineral grains. The above definition of the specific surface area is commonly used in clay science. A few authors, however, use an alternative definition and express it as total surface area per unit volume. The dimension, in that case, is L2 /L3 = L−1 , and the SI unit is m−1 . The specific surface area of a mineral grain depends on its shape, as illustrated in the following example. Let us consider three mineral grains, having the same mass and same density, therefore the same volume (Fig. 1.10). A structure of cubic grain (having equidimensional habit) is shown in Fig. 1.10a. Each side of this grain has a length of x unit. The volume is, therefore, x 3 , and the total area is 6x 2 . If its density is ρ, then its mass is x 3 ρ and the specific surface area is 6x 2 /x 3 ρ = 6/xρ. Figure 1.10b shows along grain (elongated/ prismatic/ columnar habit), having length = 4x, width = x/2 and thickness = x/2 units. The volume is, therefore, x 3 , and the total area is (2 × 4x × x/2) + (2 × 4x × x/2) + (2 × x/2 × x/2) = 8.25x 2 . If its density is ρ, then its mass is x 3 ρ and the specific surface area is 8.25x 2 /x 3 ρ = 8.25/xρ. A thin, flat grain (having platy/tabular/flaky habit) is shown in Fig. 1.10c, having length = 2x, width = 2x, and thickness = x/4 units. The volume is, therefore, x 3 , and the total area is (2 × 2x × x/4) + (2 × 2x × x/4) + (2 × 2x × 2x) = 10x 2 . If its density is ρ, then its mass is x 3 ρ and the specific surface area is 10x 2 /x 3 ρ = 10/xρ. Therefore it can be inferred that the mineral grains with flaky habits have the largest specific surface areas. As described in the previous section, the clay mineral

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Fig. 1.10 Variation of specific surface area in the mineral grains with same volume but different shapes. a A cubic grain, with equal length, width and thickness. b An elongated grain, having equal width and thickness, and length much greater than them. c A thin, flat grain, having the same length and width, which are much greater than thickness

grains have a strong tendency to break easily parallel to their interlayer planes in between any two t–o–t layers, giving rise to fine, flaky particles. The thickness of such a mineral grain is much less than its length and breadth. They, therefore, have much higher specific surface area than the nearly equidimensional minerals grains of quartz, garnet, etc. or elongated mineral grains like amphibole, tourmaline, etc. Different methods can be used to measure the specific surface area of a clay specimen, and dissimilar values may be obtained from them. When calculated from crystallographic data, the specific surface area of pure montmorillonite is measured to be ~800–810 m2 /g, of which the basal plane contributes 760 m2 /g, and the remaining 40–50 m2 /g comes from the edges (Ammann 2003). Larger specific surface areas provide a greater area of contact between a mineral and its surrounding medium, which significantly enhances the interaction and exchange of constituents between minerals and the fluid media surrounding them. Some of the physical processes (such as adsorption) or chemical reactions taking place at the surfaces of clay minerals are very important in their anti-microbial and anti-toxin actions. The specific surface area of a clay mineral is, therefore, one of the major determinants of its therapeutic and environmental applications. Some natural clays have very effective anti-bacterial actions, while some others are nonantibacterial. Among the physical and chemical attributes of the anti-bacterial clays,

1.5 Colour of Clay Minerals Table 1.1 The specific surface areas of some common clay mineral species and groups, after Kumari and Mohan (2021)

15 Mineral

Specific surface area (m2 /g)

Kaolinite

5–40

Halloysite (Hydrated)

1100

Illite

10–100

Smectite

40–800

Vermiculite

760

Palygorskite–Sepiolite

40–180

it has been observed that they comprise minerals with larger specific surface areas in greater proportions, and are much finer-grained than their non-antibacterial counterparts (Williams and Haydel 2010; Williams et al. 2011). Both of these attributes contribute to increasing the total surface area of their constituent mineral grains, thus enhancing their antibacterial actions. The mechanisms of these antibacterial actions have been comprehensively explained in Chap. 2, Sect. 2.2. The specific surface areas of some common clay minerals are given in Table 1.1. It may be noted here that the impurities present in the natural clay samples may change their specific surface areas significantly.

1.5 Colour of Clay Minerals The colour of a natural mineral, in its impure form, depends mainly on the following three factors (after Klein 2002; Nesse 2000; Putnis 1992): (i)

Chemical constituents: In some cases, the colour of a mineral is its fundamental property, directly related to one or more of its chemical constituents. The colour of such a mineral does not vary from specimen to specimen—all the specimens of that mineral show a characteristic colour. These minerals are known as idiochromatic and include some common species of clay minerals like vermiculite. (ii) Crystal structure, bond types and crystal defects: Crystal structure and bond types are important controlling factors of all types of minerals, e.g., diamond and graphite are both composed of C atoms. But they have different colours, due to the differences in the arrangement and bonding of C atoms in them. The crystal defects, like the anion vacancies, cation vacancies or other types of point defects, act as a colour centre and impart a characteristic colour to the minerals. (iii) Impurities: Impurities can influence the colour of a mineral to a great extent, especially when it is colourless or white in its pure form. Since the nature and concentration of impurities may vary widely from specimen to specimen, the colour of these minerals also varies to a large extent. Such minerals are known as allochromatic and include most of the common clay mineral species like

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1 An Overview of the Clay Minerals: Composition, Classification …

kaolinite, halloysite, illite, etc. Pure kaolinite, for example, is white, but in natural specimens, its colour may vary from off-white to cream and pale-yellow. With the increase in the concentration and the type of impurities, kaolinites can also be stained in various shades of tan, brown, blue, etc. Ions or groups of ions that produce characteristic colours in minerals are called chromophores. They give the characteristic colour in most metallic and some nonmetallic minerals. The most common chromophores are the transition elements such as Ti, V, Cr, Mn, Fe, Co, Ni and Cu. They belong to the 4th Period, B Subgroup of the periodic table. In the idiochromatic minerals, the chromophores are present as major constituent elements (e.g., Fe in vermiculite) and are responsible for their characteristic colour; while in the allochromatic minerals, they are present as impurities and are responsible for the variation in colour. Due to the antimicrobial properties of clay minerals, there are recommendations to produce virus-resistant disinfectants from them (see Chap. 6 for a detailed discussion on this subject). Das and Tadikonda (2020) suggested using clay-based disinfectants as alternatives to conventional detergents to wash medical gear. Such disinfectants must be produced from purified allochromatic clay minerals that are colourless. An idiochromatic clay mineral may stain the clothes with its own characteristic colour, while an allochromatic clay mineral with impurities may stain the clothes with the colour of the chromophores it contains. Both of them are therefore useless for washing purposes. The colours of some common clay minerals, in their pure forms, are given in Table 1.2 (after Anthony et al. 2003). The websites referred to in this table contain excellent collections of coloured photographs of the respective clay minerals. Table 1.2 The colours of some common clay mineral, without any impurities

Mineral

Colour (in pure form) Reference

Kaolinite

White

https://www.mindat. org/show.php?id= 2156

Halloysite

White

https://www.mindat. org/min-1808.html

Illite

White (gray-white to silvery white)

https://www.mindat. org/min-2011.html

Montmorillonite

White or light buff

https://www.mindat. org/min-2821.html

Vermiculite

Brown or bronze

https://www.mindat. org/min-4170.html

Palygorskite

White (greyish or yellowish white)

https://www.mindat. org/min-3072.html

Sepiolite

White (greyish or yellowish white)

https://www.mindat. org/min-3621.html

1.6 Cation Substitution and Cation Exchange Capacity (CEC) of Clay Minerals

17

1.6 Cation Substitution and Cation Exchange Capacity (CEC) of Clay Minerals The internal structure of a mineral may be considered as a three-dimensional network of ions extended in all directions. Any ion in that structure may be replaced or substituted by another ion with a similar radius and charge, without causing a serious distortion in the structure. This is known as ionic substitution or diadochy. A mineral, when in its pure form, is composed of some particular ions occupying specific lattice positions. But when the same mineral comes into contact with a solution of other ions having similar size and charge, those other ions can be incorporated into the structure of that mineral, substituting its original ions. The t–o–t layers in the clay minerals of illite, smectite and vermiculite groups commonly have a net negative charge for the following two reasons: (a) The substitution of Si4+ by Al3+ in the tetrahedral cationic sites (b) The substitution of the trivalent or bivalent octahedral cations by other cations of lower charge. The electrical neutrality of these minerals is maintained by the incorporation of a small number of alkali metal or alkaline earth cations in the interlayer spaces between two t–o–t layers. As explained in the preceding Sect. 1.3 (ii), the characteristic t–o– t–c structure in these mineral groups is produced in this way. The common interlayer cations in illites are K+ , in smectites, they are Ca2+ and Na+ , and in vermiculite, it is Mg2+ . The clay minerals of the above three groups, however, have a stronger affinity for heavy metal cations, like Cu2+ , Pb2+ , Zn2+ , Cd2+ , Mn2+ , etc., than for the alkali and alkaline earth cations (Tiller 1996). As a result, when these clay minerals come into contact with an aqueous solution containing the heavy metal cations, there may be cationic substitution in their interlayer spaces, in which the original interlayer cations are replaced by the newly introduced heavy metals. This gives rise to a cation exchange between the clay minerals and the surrounding liquid, the phenomenon that is very important in the antitoxin application of the clay minerals. The removal of heavy metal toxins from a solution by cation exchange, along with the therapeutic and environmental applications of this process, has been elucidated in the succeeding chapters. The cation exchange capacity (CEC) of a clay mineral is defined as the number of moles of positive charge it can absorb per unit mass (after Raymond and Brady 2016). It is commonly expressed in the following two units: • Milliequivalents per 100 g (meq/100 g) • Centimoles of charge per kilogram (cmolc/kg). The equivalent weight (Eq) of an element is its gram atomic weight divided by its valence. One equivalent weight of that element combines with or displaces 1.008 g of hydrogen or 8.0 g of oxygen or 35.5 g of chlorine. For example, the equivalent

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weight of an oxygen atom or O– 2 ion is 16.0 g/2 = 8.0 g, since its atomic weight is 16 and the usual valence is 2. One milli equivalent (mEq) is one-thousandth (part) of the equivalent weight of an element or a compound, i.e., 1 mEq = 1/1000 Eq. The mole (mol) is the SI unit of amount of substance, defined as the amount of that substance containing exactly 6.02214076 × 1023 elementary entities, i.e., atoms, molecules, or ions. The mass of one mole of a chemical substance in grams is numerically equal, for most practical purposes, to the average mass of one molecule of that substance. In other words, if the molecular weight of an element is x, then one mole of that element weighs x gram. For example, one mole of an oxygen atom or O−2 weighs 16 g. One centimole (cmol) is one-hundredth of one mole of a substance (i.e., 1 cmol = 1/100 mol). Relation between the two units −mEq/100 g and cmol/kg: One mole of a given ion is equal to its one equivalent weight multiplied by its valence. For the monovalent cations like Na+ , K+ , Mn+ etc., 1 mol = 1 equivalent weight. Therefore, for these cations. [ ] 1 cmol/kg = [(1/100 mole)]/ 1000 g [ ] [ ] = 1/100 × 1 Eq / 1000 g = 1 mEq/100 g For the bivalent cations like Ca2+ , Fe2+ , Mg2+ etc., 1 mol = 2 equivalent weight. Therefore for these cations, [ ] 1 cmol/kg = [(1/100 mole)]/ 1000 g [ ] [ ] = 1/100 × 2 Eq / 1000 g = 2 mEq/100 g For the trivalent cations like Al3+ , Fe3+ etc., 1 mol = 3 equivalent weight. [ ] 1 cmol/kg = [(1/100 mole)]/ 1000 g [ ] [ ] = 1/100 × 3 Eq / 1000 g = 3 mEq/100 g The cation exchange capacities of some common clay minerals are given in Table 1.3. The t–o layers that build up the internal structure of kaolinite are electrically neutral. However, a small net negative charge may develop in them, caused by the limited substitution of Si4+ by Al3+ in the tetrahedral cationic site, or by the substitution of Al3+ by some bivalent cation in the octahedral cationic site. The small negative charge thus developed is the reason for the low CEC of kaolinite given in

1.6 Cation Substitution and Cation Exchange Capacity (CEC) of Clay Minerals Table 1.3 The cation exchange capacities (CEC) of some common clay mineral species and groups, after Kumari and Mohan (2021)

Mineral

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CEC (mEq/100 g)

Kaolinite

3–15

Halloysite (Hydrated)

40–50

Illite

10–40

Smectite

80–120

Vermiculite

100–150

Palygorskite–Sepiolite

32 –0

Table 1.3. Ferris and Jepson (1975) studied elaborately the cation exchange capacity of kaolinite and commented that, unlike the other common clay minerals, kaolinite did not have a definite CEC. Their investigations revealed that the cation uptake of kaolinite depends upon the following factors: (i)

The type of cation: The cation uptake capacity of kaolinite is not the same for different cations. Experiments with the aqueous solutions of chloride salts of different cations, at a constant pH of 7, indicate that the cation adsorption decreases in the following order: Ca2+ > Cs+ > Na+ > Li+

(ii) The electrolyte concentration in the solution: Other conditions remaining the same, the uptake of a particular cation decreases with the decrease of the concentration of the electrolyte salt of that cation. This was shown by the conspicuous decrease in Na+ adsorption with decreasing concentration of NaCl in the solution at a constant pH of ~7.0. (iii) The pH of the solution: Other factors remaining the same, the adsorption of cations by kaolinite increased significantly with the increase of pH. Simultaneously, there was a conspicuous decrease in the anion uptake with the increase of pH. This was proved by the increase in Na+ adsorption and decrease in Cl− adsorption from pH = 2 to pH = 12. (iv) The type of solvent: The adsorption of cations is significantly greater on kaolinite suspended in 95% ethanol than that in water, as indicated by the increased uptake of Na+ on kaolinite in ethanol medium. The non-hydrated form of halloysite has a composition similar to kaolinite, and its CEC does not differ much from that of kaolinite. But in the hydrated form, with a single layer of water introduced between unit kaolinite layers, incorporation of cations may occur in the interlayer space. This is the reason for the higher CEC of hydrated halloysite than kaolinite, as shown in Table 1.3. The CEC of illite lies between those of kaolinite and the smectite group minerals. Although substitution of cations in the tetrahedral and the octahedral sites may result in a significant net negative charge in someillites, the K+ in the interlayer spaces balance the charges and strongly bond the adjacent t–o–t layers together. As a result,

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illite has intermediate values for surface area (Table 1.1), and also for cation exchange capacity (Table 1.3). In the smectite group minerals, the bond holding the t–o–t layers together is the weak Van der Waals forces and some exchangeable cations. This very weak bond can be easily broken by water or other polar or cationic organic fluids entering the interlayer spaces. A substantial net negative charge may develop in the t–o–t layers of many smectites due to extensive substitution of cations in the tetrahedral and octahedral cations, which results in their high cation exchange capacity. In the minerals of the vermiculite group, the substitution of Si4+ by Al3+ in the tetrahedral sites is extensive in the tetrahedral sheet, resulting in a high net negative charge on the crystal surface. This net negative charge, which is generally balanced by the incorporation of bivalent cations like Mg2+ and Ca2+ in the interlayer spaces, is greater than that of the smectite group minerals. For this reason, the vermiculite group minerals have the highest cation exchange capacity among the clay minerals (Deer et al. 1992).

1.7 Clay Mineral as Adsorbents of Organic and Inorganic Substances Adsorption is the property of a solid substance to attract, bind, and accumulate molecules or particles to its surface, thus forming a condensed layer to its surface (after Williams and Haydel 2010). The solid substances that can absorb other substances are called adsorbents, and absorbed molecules or particles are called adsorbates. It is to be noted that adsorption is different from absorption, which refers to the diffusion or penetration of a substance into a liquid or solid forming a transition zone or layer, often with a new composition, adjacent to the substrate. Clay minerals, owing to their characteristic internal structures and chemical compositions, are capable of adsorbing a wide range of substances. The adsorption capacity of a clay mineral depends on a number of controlling factors, including its specific surface area, ion exchange capacity, charge density on the surface, the size of the adsorbate particles, and the roughness of its surface. An even surface of the adsorbent provides the same area for adsorption of the small and the large adsorbate particles, while an uneven surface with pores, holes, etc. provides a greater area of adsorption to the smaller particles (Ammann 2003; Helmy et al. 1998). The viruses, being very small, are easily adsorbed by clay flakes as the latter provides a greater surface area that promotes their adsorption. The bacteria, in contrast, are much larger than the viruses and are not easily adsorbed, in fact, they are destroyed by the clays through a series of chemical reactions. See Sect. 2.2.1 of Chap. 2 for details. The inter-layer spaces of many clay mineral species, especially those belonging to the smectite and vermiculite group, can incorporate heavy metal cations, as explained in Sect. 1.5. This property enables them to remove metallic toxins from a solution.

1.7 Clay Mineral as Adsorbents of Organic and Inorganic Substances

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Kaolinite, on the other hand, has replaceable hydroxyl ions on the surfaces of its structural t–o layers, which enable it to exchange anions with a substrate. It has a higher anion exchange capacity than the other clay minerals and can absorb certain cations (Deer et al. 1992). Many clay minerals, especially those belonging to the smectite and vermiculite groups can also adsorb a wide variety of organic molecules, a few examples of which are given below. (i) (ii) (iii)

Organic pollutants like 2, 4, 6- trichlorophenol (Chen et al. 2011). Paraffin and aromatic molecules of petroleum (Cosultchi et al. 2004). Organic molecules of metanil yellow dye, p-aminodiphenylamine, and benzidine (Gemeay et al. 2002). (iv) Polypeptide like polylysine and polyglutamic acid (Gougeon et al. 2003). (v) Fatty acids like stearic and oleic acids (Khalil and Abdelhakim 2002). (vi) Humicand fulvic acids (Naceur et al. 2004). (vii) Organophosphates like dimethyl-methyl phosphonate and diethyl-ethyl phosphonate were used as nerve agents in chemical warfare (Plachá et al. 2019). (viii) Divalent organic cations paraquat and diquat (Rytwo et al. 1996). (ix) A group of organic pesticides including 2,4–dichlorophenoxyacetic acid or 2,4–D (Sannino et al. 1997). In some of the above cases, synthetic clay derivatives with hydrophobic and organophilic properties are more effective than hydrophilic natural clay minerals. The mechanism for binding the organic molecules onto the surfaces of clay particles is given in Chap. 2, Sect. 2.1. The minerals of the palygorskite-sepiolite group have large volumes of vacant spaces in between the chains of cationic octahedral that are linked to the tetrahedral sheets. These tubular vacant spaces can accommodate a wide range of foreign particles. The palygorskite-sepiolite group minerals, therefore, can adsorb a wide range of inorganic or organic toxin molecules and pathogens, which is one of the most important attributes of clay minerals in their antimicrobial and antitoxin actions. Concluding Remarks The clay minerals, which are the major constituents of the natural clays, belong to the phyllosilicate subclass of silicate class; and are divided into six groups: kaolinites, illites, smectites, vermiculites, palygorskite-sepiolite, and mixed-layer clays. The compositions and internal structures of these clay mineral groups have been explained in this chapter, which will help the readers to understand their antimicrobial and antitoxic applications and the physico-chemical reactions described in the next chapters. The clay minerals, owing to their distinctive compositions and internal structures, have a number of mineralogical, physical and chemical properties, including their specific surface area, colour, cation substitution and cation exchange capacity, and the ability to adsorb different types of organic and inorganic substances. All these properties, which make them suitable for the antimicrobial and

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antitoxic applications described in this book, have also been explained briefly in this chapter.

References and Further Reading Anthony, J.W., Bideaux, R.A., Bladh, K.W. and M.C. Nichols Eds. (2003). Handbook of Mineralogy, Mineralogical Society of America, Chantilly, VA 20151-1110, USA. http://www.handbookofmi neralogy.org/. Ammann, L. (2003). Cation exchange and adsorption on clays and clay minerals. Dissertation Submitted for the degree “Dr. rer. nat.” of the faculty of mathematics and natural sciences Christian-Albrechts-University, Kiel. 1–113. Bergaya, F., Theng, B.K.G. and G. Lagaly (2006). Clays in Industry. In: Bergaya, F., Theng, B.K.G. and G. Lagaly (Eds), Handbook of Clay Science. Elsevier, Amsterdam. Chen, J., Liua, X., Li, G., Nie, X., An, T., Zhang, S. and H. Zhao (2011). Synthesis and characterisation of novel SiO2 and TiO2 co-pillaredmontmorillonite composite for adsorption and photocatalytic degradation of hydrophobic organic pollutants in water. Catalysis Today, 164 (2011): 364–369. Cosultchi, A., Bosch, P. and V.H. Lara (2004). Adsorption of petroleum organic compounds on natural Wyoming montmorillonite. Colloids and Surfaces A: Physicochem. Eng. Aspects, 243: 53–61. Dana, J.D. and W.E. Ford (1915). Dana’s Manual of Mineralogy for the Student of Elementary Mineralogy, the Mining Engineer, the Geologist, the Prospector, the Collector, Etc (13 Ed.). John Wiley & Sons, Inc. pp. 299–300. Das, P. and B.V. Tadikonda (2020). Bentonite clay: A potential natural sanitizer for preventing neurological disorders. American Chemical Society Publication, Chemical Neuroscience, https:// doi.org/10.1021/acschemneuro.0c00609. Deer, W.A., Howie, R.A. and J. Zussman (1992). An introduction to the rock forming minerals. English Language Book Society with Longman. Eberl, D.D. (1984). Clay mineral formation and transformation in rocks and soils. Phil. Trans. R. Soc. Lond. A, 311: 2412–2457. Filomena, S., Violante, A. and G. Liliana (1997). Adsorption-Desorption of 2,4–D by hydroxy aluminium montmorillonite complexes. Pestic. Sci., 51: 429–435. Folk, R.L. (1974). Petrology of sedimentary rocks. Hemphill Publishing Co., Texas. Gemeay, A.H., El-Sherbiny, A.S. and A.B. Zaki (2002). Adsorption and kinetic studies of the intercalation of some organic compounds onto NaC-montmorillonite. Journal of Colloid and Interface Science, 245: 116–125. https://doi.org/10.1006/jcis.2001.7989 Ghosh, B. (2013). Clays and their constituents – Definitions and a brief overview. In: Mukherjee, S., (Ed.) The Science of Clays: Applications in Industry, Engineering and Environment. Gougeon, R.D., Soulard, M., Reinholdt, M., Miehe-Brendle, J., Chezeau, J., Dred, R.L., Marchal, R. and P. Jeandet (2003). Polypeptide adsorption on a synthetic montmorillonite: A combined solid state NMR Spectroscopy, X-ray diffraction, thermal analysis and N2 adsorption study. Eur. Journal of Inorganic Chemistry, 1366–1372. Guggenheim, S. and R.T. Martin (1995). Definition of clay and clay mineral. Joint report of the AIPEA nomenclature and CMS nomenclature committees. Clays and Clay Minerals, 43(2): 2552–2556. Guggenheim, S. and R.T. Martin (1996). Reply to the comment by D. M. Moore on “Definition of clay and clay mineral: Joint report of the AIPEA nomenclature and CMS nomenclature committees”. Clays and Clay Minerals, 44(5): 713–715. Guggenheim, S., Adams, J.M., Bain, D.C., Bergaya, F., Brigatti, M.F., Drits, V.A., Formoso, M.L.L., Galan, E., Kogure, T. and H. Stanjek (2006). Summary of recommendations of nomenclature

References and Further Reading

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committees relevant to clay mineralogy: Report of the Association Internationale pour l’Etude des Argiles (AIPEA) Nomenclature Committee for 2006. Clays and Clay Minerals, 54: 761–772. Halloysite https://www.mindat.org/min-1808.html. Last visited: 16th November, (2021). Harvey, C.C. and G. Lagaly (2006). Conventional applications. In: Bergaya, F., Theng, B.K.G. and G. Lagaly (Eds), Handbook of Clay Science. Elsevier, Amsterdam. Harvey, C.C. and H.H. Murray (1993). The geology, mineralogy and exploitation of halloysite clays of Northland, New Zealand. In: Murray, H.H., Bundy, W.M. and C.C. Harvey (Eds), Kaolin Genesis and Utilization. The Clay Minerals Society. Hawthorne, F.C., Uvarova, Y.A. and E. Sokolov (2019). A structure hierarchy for silicate minerals: Sheet silicates. Mineralogical Magazine, 83: 3–55. Helmy, A.K., Ferreiro, E.A., de Bussetti, S.G. and N. Peinemann (1998). Surface areas of kaolin, a-Fe2 O3 and hydroxy-Al montmorillonite. Colloid and Polymer Science, 276: 539–543. Illite, https://www.mindat.org/min-2011.html. Last visited: 16th November, (2021). Jiangyao, C., XiaoluLiua, Guiying Li, Xin Niea, Taicheng Ana, Shanqing Zhang, Huijun Zhao, (2011). Synthesis and characterization of novel SiO2 and TiO2 co-pillared montmorillonite composite for adsorption and photocatalytic degradation of hydrophobic organic pollutants in water. Catalysis Today, 164: 364–369. Kaolinite, https://www.mindat.org/show.php?id=2156. Last visited: 16th November, (2021). Khalil, H.S.A. and Abdelhakim, A.A. (2002). Adsorption studies of fatty acids on montmorillonitebased filler clay. Journal of Applied Polymer Science. 86: 2574–2580. Klein, C. (2002). Mineral Science. John Wiley & Sons, Inc. Kumari, N. and C. Mohan (2021). Basics of clay minerals and their characteristic properties. Clay and Clay minerals (Edited by Gustavo Morari Do Nascimento). https://doi.org/10.5772/intech open.97672. Mason, B.H. and C.B. Moore (1982). Principles of Geochemistry, Wiley. Millot, G. (1970). Geology of Clays. Translated by W. R. Farrand and H. Paquet. Springer Verlag. Montmorillonite, https://www.mindat.org/min-2821.html. Last visited: 16th November (2021). Moore, D.M. (1996). Comment on: Definition of clay and clay mineral: Joint Report of the AIPEA Nomenclature and CMS Nomenclature Committees. Clays and Clay Minerals, 44: 710–712. Naceur, M.W., Messaoudene, N.A., Megatli, S. and A. Khelifa (2004). Organic matter adsorption on montmorillonite pillared by an organophile complex for tangential microfiltration through a ZrO2 -TiO2 inorganic membrance. Desalination, 168: 253–258. Nesse, W.D. (2000). Introduction to Mineralogy. Oxford University Press. Ollier, C. (1984). Weathering (2nd edition). Geomorphology Texts. Longmans, London. Palygorskite, https://www.mindat.org/min-3072.html. Last visited: 17th November, (2021). ˇ Plachá, D., Kováˇr, P., Van˘ek, J., Mikeska, M., Škrlová, K., Dutko, O., Rehaˇ cková, L. and J. Slabotínský (2019). Adsorption of nerve agent simulants onto vermiculite structure: Experiments and modelling. Journal of Hazardous Materials, 382: 121001. https://doi.org/10.1016/j.jhazmat. 2019.121001. Putnis, A. (1992). Introduction to Mineral Sciences. Cambridge University Press. Régis, D. Gougeon, R.D., Michel Soulard, M., Marc Reinholdt, M., Miehé-Brendle, J., Chézeau, J.-M., Le Dred, R., Marchal, R. and P. Jeandet (2003). Polypeptide adsorption on a synthetic montmorillonite: A combined solid-state NMR spectroscopy, X-ray diffraction, thermal analysis and N2 adsorption study. Eur. J. Inorg. Chem., 2003: 1366–1372. Rytwo, G., Nir, S. and L. Margulies (1996). A model for adsorption of divalent organic cations to montmorillonite. Journal of Colloid and Interface Science, 181: 551–560. Sannino, F., Violante, A. and L. Gianfreda (1997). Adsorption-desorption of 2, 4-D by hydroxyl aluminium montmorillonite complexes. Pestic. Sci., 51: 429–435. Sepiolite, https://www.mindat.org/min-3621.html. Last visited: 17th November, (2021). Tiller, K.G. (1996). Soil contamination issues: Past, present and future, a personal perspective. In: Naidu, R., Kookana, R.S., Oliver, D.P., Rogers, S. and McLaughlin, M.J. (Eds.). Contaminants and the Soil Environment in the Australasia-Pacific Region. Kluwer, Dordrecht. Tucker, M.E. (1981). Sedimentary petrology: An introduction. Blackwell Scientific Publications.

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Velde, B. (1980). Clay minerals: A physico-chemical explanation of their occurrence. Elsevier. Vermiculite, https://www.mindat.org/min-4170.html. Last visited: 16th November, (2021) Ray R. and N.C. Brady (2017). The Nature and Properties of Soils, 15th Edition. Pearson Education Limited.

Chapter 2

Clay-Induced Antimicrobial and Antitoxic Mechanisms: How Do the Clays Protect Us from Pathogens and Toxins?

Introduction The socio-economic applications of a substance depend on its physical and chemical properties, which, in turn, are determined by its internal structure and chemical composition. The previous chapter discussed the structures and compositions of the clay minerals and their consequent properties. This chapter endeavours to explain the antimicrobial and the antitoxin potentialities of the clay minerals in the light of their physico-chemical properties, structures and compositions. The present state of knowledge, however, does not provide us with a comprehensive explanation for all the antimicrobial aspects of clays; neither can we correlate all their medicinal applications with their distinctive compositions and structures. Nevertheless, a host of investigations carried out on this line indicate that clay minerals can sequester some types of pathogens, mainly viruses, by adsorption, and play an important role in the bactericidal mechanism of iron, copper and other metals. However, the question arises that why the other phyllosilicates, in spite of having t–o–t–c structures like clay minerals, cannot remove the toxins and microbes from a solution? And, why many other minerals rich in ferrous iron and other metals are not bactericidal like the clay minerals? These two issues are addressed in the following Sects. 2.1 and 2.2, respectively. Section 2.3 briefly describes the antimicrobial mechanism of some clay derivatives, which are synthesised by loading newly introduced bactericidal cations in clay interlayer spaces. The mechanisms by which the clay minerals remove organic toxins from a system have been explained in Sect. 2.4.

2.1 Clays Protecting from Viral Infections: The Mechanism of Virus Adoption It has been recognised more than fifty years ago that the removal of the virus is caused by the physical presence of the clay, not by the action of a chemical substance obtained from the clays (Carlson et al. 1968); and the viruses are readily adsorbed © Capital Publishing Company, New Delhi, India 2023 B. Ghosh and D. Chakraborty, Clay Minerals, https://doi.org/10.1007/978-3-031-22327-3_2

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on the surfaces of clay particles. Adsorption of water, inorganic or organic toxin molecules and pathogens is one of the most distinguishing attributes of the clay minerals that facilitates a wide range of their therapeutic, industrial and environmental applications. The process of adsorption, as described in Chap. 1, Sect. 1.7, involves the adhesion of particles like atoms or ions, organic or inorganic molecules, cells of microorganisms, etc. to the surface of a solid. The size of the viruses is much smaller than the other types of microorganisms like bacteria, fungi, protozoa, etc. For this reason, the surface area provided by an uneven surface for the adsorption of viruses is much greater than that for the other pathogens, and they are adsorbed more readily by suspended clay flakes in a liquid medium. But it must be noted here that, viruses are not destroyed by adsorption, and they can cause diseases even when adhered strongly to the surface of clay minerals. Lipson and Stotsky (1986) observed that poliovirus, rotavirus, and reovirus were still infectious after they were adsorbed on the clay particles of soil; and laboratory experiments further revealed that in a few cases, the virions adsorbed to clay particles had higher infectivity levels than those which were not adsorbed. This has also been reported by many other workers (for example, Floyd and Sharp 1978; Lipson and Stotsky 1983; Schaub et al. 1974; Shirobokov 1973; Sykes and Williams 1978) in their investigations performed with a wide range of viruses and adsorbent materials (including clay minerals). Then the question arises: how can the clays protect human health and the environment from viruses? The plausible answers are explained below. (a) One of the protective actions of the clays is based on their tendency to form coagulates or flocs in an aqueous medium in presence of electrolytes. The viruses that are adsorbed to the clay particles, though still infectious, are trapped in the flocs. The process of floc formation and virus entrapment has been discussed in Sect. 2.1.2 of this chapter. The viruses adhered to the clay can thus be removed from a system by removal of the floc. Although the isolated viruses in a liquid medium are small enough to pass through a bacteria filter or remain suspended for a long time, those adhered strongly to the clay particles in the coagulate can be separated by filtration, or settle down to the bottom of the medium by decantation, which makes the liquid medium free of the viruses. (b) Furthermore, a large number of viruses are rendered much less infectious when adsorbed on clay particles. Block et al. (2016) reported that the influenza virus aggregated to the clay particles was at a lower infectivity level than the nonaggregated virus. They explained that the infectivity was reduced upon aggregation because each pellet of virus–clay aggregate acted as a single infectious unit. Given that each aggregate pellet contained ~102 virus particles, they estimated a nearly 102 -fold reduction of infectivity upon aggregation. The process of adsorption, therefore, plays a central role in the protective actions of clays against the viruses, and it is, therefore, necessary to delve deeper into this process for furthering their antiviral applications. The virus absorption mechanism of the clays, however, is yet to be fully understood; and incompatible results have been reported by different workers regarding the importance of some of the possible

2.1 Clays Protecting from Viral Infections: The Mechanism of Virus Adoption

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controlling factors. This section presents a comprehensive description of all the factors that may influence the adsorption mechanism to various extents, along with the conforming or noncompliant views of different workers in this regard. Simple, easily understandable explanations are provided for all the processes and factors involved wherever needed.

2.1.1 The Role of Cations in the Adsorption Mechanism Carlson et al. (1968) studied the mechanism of the removal of bacteriophage T2 (coliphage, that kills the bacteria Escherichia coli) and type 1 polio virus by kaolinite, montmorillonite, and illite. Their investigations established that the cations present in an aquatic system play an important role in the adsorption mechanism. The salient features of their findings are explained below. (a) Concentration of cations in the system: The adsorption of viruses on clay particles depends on the concentration of different types of cations in the system. When the clay concentration is constant and the concentration of Na+ or Ca2+ increases, the virus removal increases correspondingly. (b) Comparative effectiveness of different cations in the adsorption process: In a given system, the maximum level of virus inactivation by Na+ was found to be higher than that by Ca2+ . (ii) To reach that maximum level of virus inactivation, a lower concentration of Ca2+ is needed than Na+ : 10 times more Na+ is needed than Ca2+ to bring about the maximum virus adsorption. (iii) Al3+ could bring about 98% removal of virus particles in concentrations as low as 0.000005 M. (i)

(c) The clay-cation-virus bridge: The cations present in the system connect the clay particles to the virus, just as two landmasses are connected by a bridge in between them. This linking is referred to as the clay-cation-virus bridge. The virus thus linked to the clay can be removed from a system by the removal of clay particles.

2.1.2 Flocculation and the Virus Adsorption Mechanism Flocculation (also called agglomeration or coagulation) is the process during which particles suspended or dispersed in a liquid come in contact with one another, and adhere together to form clusters or lumps of larger size known as floc or coagulate. Clay particles usually possess a net negative charge (at their interlayer spaces), therefore, they electrostatically attract different types of cations, such as Ca2+ , Na+ , etc., which form bridges, holding the clay particles together. In the presence of

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these cations, clay particles adhere together to form large clusters, leading to the flocculation of clay (after Chibowski 2011). Flocculation power of a cation is indicated by how fast it can form the floc in a liquid. Different cations have different flocculation powers—those having higher valences have greater flocculation powers. For example, among the three cations Al3+ , Na+ and Ca2+ , flocculation power of Al3+ and Na+ are highest and lowest respectively, i.e., Al3+ > Ca2+ > Na+ . This has been stated in the Schulze-Hardy rule: Greater the valency of the oppositely charged ion of the electrolyte added, the faster is the coagulation. The classical Schulze-Hardy rule suggests that the critical coagulation concentration (CCC) decreases as the inverse sixth power of the counterion valence (after Trefalt et al. 2020). [Counterion: an ion having a charge opposite to that of the substance with which it is associated]. The time required for a given amount of clay to flocculate is largely influenced by the cation concentration in the system: generally, an increase in the cation concentration causes faster flocculation. Schaub and Sagik (1975) studied the effects of montmorillonite (with cation capacity of 80–100 meg/100 g) on two encephalomyocarditis (EMC) viruses, Columbia SK and mengovirus, and explained the virus adsorption in terms of colloids chemistry, assuming that the flocculation of clay in presence of cations takes place in accordance with the Schulze-Hardy rule. The montmorillonite they used had high CEC, which flocculated following the Schulze-Hardy rule. The mechanism of virus adsorption by clay, as suggested by them, is explained below: (i)

Virus entrapment during flocculation was not a significant mechanism for additional removal of virus from suspension, because previously formed flocs, when dispersed again in the system, can equally adsorb the virus that is added later to the system. This indicates that after flocculation, there was no significant decrease in the number of adsorption sites that entrap the virus. (ii) However, if the proportion of virus in the system gradually increases, then solids coagulation before contact with the virus may reduce total adsorption since the adsorption sites enclosed in the floc are less accessible to the virus-containing liquid. (iii) The size of the particles to be adsorbed or adhered to the clay surface is an important factor for the adsorption mechanism: the smaller particles are attached more easily to the clay. It is therefore likely that the relatively small virus particles have a much greater chance of remaining attached to a clay particle than another clay particle. (iv) Virus adsorption before flocculation: A significant finding of the studies of Schaub and Sagik (1975) is that flocculation took place in the montmorillonite clay system 30 min after cation addition, but the virus was adsorbed before that. The above observation indicates that the formation of a clay-cation-virus bridge is not the only factor responsible for virus adsorption by clay, and physical processes like the Van der Waals forces and hydrogen bonding also contribute significantly to the adsorption mechanism. The comments of Lipson and Stotzky (1983) on the studies of Schaub and Sagik (1975) may be referred to in this regard.

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2.1.3 The Importance of CEC of Clays in Virus Adsorption The adsorption of viruses primarily occurs in the negatively charged sites in the internal structures of the clay minerals. The cation exchange capacity (CEC) of the clay minerals (described in details in Chap. 1, Sect. 1.6), plays an important role in their virus adsorption mechanism. This has been established independently from a substantial number of investigations in the last 50–60 years, performed on a wide range of viruses, and with different types of clay minerals. The results of some of those works are chronologically listed below. • Drewry and Eflassen (1968) studied the adsorption mechanism of T1, T2, and f2 viruses by montmorillonite. • Carlson et al. (1968) studied the adsorption of bacteriophage T2 (coliphage, that kills Escherichia coli) by kaolinite, montmorillonite, and illite. • Burge and Enkiri (1978) studied the adsorption mechanism of coliphages by clay in the soil. • Funderberg et al. (1981) studied the adsorption mechanism of T1, T2, and f2 viruses by montmorillonite. • Ostle and Holt (1979) studied the adsorption mechanism of a type of bacteriophage by montmorillonite. • Lipson and Stotzky (1983) studied the mechanisms involved in the adsorption of reovirus type 3 by kaolinite and montmorillonite. Conversely, Goyal and Gerba (1979) found no relationship between the CEC of clay (in different types of soil) and the adsorption of a number of enteroviruses, coliphages, and Simian rotavirus. But some inaccuracies in their experimental procedures have been pointed out by Lipson and Stotzky (1983), which might lead to this erroneous conclusion. The property of clay minerals to adsorb pathogens, organic or inorganic molecules, and many of their other surface chemical properties, may vary significantly with the variation of the interlayer cations present in them. The clay minerals with Na+ , Ca2+ , or Al3+ in their interlayer spaces generally have dissimilar surface properties. Homoionic clay minerals (Greek homo: same + ionic) contain only one type of cation in their interlayer spaces. Most natural clay minerals, however, are heteroionic, i.e., have more than one type of interlayer cations. Homoionic clays are required to investigate all the surface chemical properties, and also to enhance the ability of adsorption of clay to make it more suitable for various antimicrobial, antitoxin and industrial applications. Different workers have proposed different methodologies for the formulation of homoionic clays from natural heteroionic clay minerals, e.g., Ferris and Jepson (1975) described the preparation of kaolinite homoionic to Na+ from natural kaolin, Steudel and Emmerich (2013) described the synthesis of montmorillonites homoionic to Na+ , Li+ , K+ , Ca2+ , Mg2+ , Cu2+ , or Zn2+ from natural and purified bentonites. Lipson and Stotzky (1983) prepared different types of clays that are homoionic to Na+ , K+ , Ca2+ , Mg2+ , and Al3+ ; and studied elaborately the quantity of reovirus

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adsorbed by each of them. Earlier, Sykes and Williams (1978) conducted similar experiments to study the adsorption of actinophage f6 virus (that kills Streptomyces sp.) by the kaolinite homoionic to different cations. The results of these investigations are described below. (a) Variation in the adsorption ability of the same clay mineral homoionic to different cations: The different homoionic clays, prepared from a given clay mineral combined with different cations, have significantly different abilities to adsorb viruses. For example, kaolinite homoionic to Na+ can easily adsorb reovirus than the kaolinite homoionic to Al3+ or Ca2+ , because it is relatively easy for the reovirus to replace the monovalent Na+ in the exchange sites of kaolinite. The cations of higher valency, like Al3+ , Ca2+ , etc. are more strongly bonded to kaolinite, and cannot be replaced easily by the virus. Lipson and Stotzky (1983) established the following sequence of homoionic kaolinites in order of decreasing amount of adsorption of reovirus: Na+ > Al3+ > Ca2+ > Mg2+ > K+ . Sykes and Williams (1978) obtained a similar result on the adsorption of actinophage by kaolinites homoionic to Na+ , Ca2+ and Al3+ . Although the relatively low adsorption of kaolinite homoionic to K+ , as reported by Lipson and Stotzky (1983), may appear to be anomalous; this may be explained by the higher bond energy of K+ due to their smaller hydrated ionic radius than that of the other cations. This results in their entrapment in the interlayer spaces of the expanding 2:1 clays lattice. The sequence of the homoionic montmorillonites in order of decreasing amount of adsorption of reovirus is Al3+ > Ca2+ > Mg2+ > Na+ > K+ . The low adsorption of reovirus to montmorillonite homoionic to K+ ions was probably the result of the collapsing of the clay lattices, which prevented the expression of the interlayer-derived CEC. (b) Variation in the adsorption ability of different clay minerals homoionic to the same cation: Kaolinite and montmorillonite homoionic to a particular cation (such as Na+ , Ca2+ , or Mg2+ ) do not absorb the same quantity of viruses—their adsorption power varies considerably. Lipson and Stotzky (1983) reported that at lower clay concentrations, montmorillonite homoionic to Ca2+ , Al3+ , Na+ , or Mg2+ adsorbed more reovirus than same quantities of kaolinite homoionic to the same cations. The higher CEC of montmorillonite than kaolinite has been stated as the probable reason for this. The high adsorption of reovirus to montmorillonite homoionic to Al3+ may have been related to the sufficient reduction of the electrokinetic potential of the particles by the polyvalent cation, in accordance with the Schulze-Hardy rule (Santoro and Stotzky 1968).

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2.1.4 Effects of Van der Waals Forces of Attraction and Hydrogen Bonding The results of the investigations by Lipson and Stotzky (1983) implied the possible involvement of these two bondings in the adsorption process. In this respect, their findings conform to those of the following earlier and later workers: • Greenland et al. (1965) explained the significance of Van der Waals forces in the adsorption of amino acids at or near their pI to clays in the absence of proton or cation exchange. • Stotzky (1980) emphasised the importance of hydrogen bonds in the binding of proteins to clays at pHb values above the pI of the proteins. • Block et al. (2016) studied the interaction between montmorillonite and influenza virus. They found that the virus readily forms aggregates with the clay particles, and suggested that the attraction causing the aggregation was not electrostatic, but might instead be hydrophobic or Van der Waals in nature. Studies with transmission electron microscopy revealed that the attraction was strong enough to cause distortion of the shape of the virus attached to the clay particles.

2.1.5 Effects of Specific Surface Area and Surface Charge Density Carlson et al. (1968) studied the virus adsorption capacities of montmorillonite, kaolinite, and illite in an aquatic suspension, in presence of NaCl and CaCl2 which provided Na+ and Ca2+ respectively in the system. They reported that the molar amounts of each salt required for maximum virus adsorption by a clay mineral were nearly equal for montmorillonite and kaolinite, but a greater amount of each salt was required for illite to reach the maximum adsorption level. But this result does not conform to the CEC of the three types of clay minerals used—the CEC of montmorillonite being much greater than those of the other two (See Chap. 1, Sect. 1.6 for details). This result led them to infer that the CEC of a clay mineral is not the only factor that is important in the virus adsorption mechanism, but its surface exchange capacity also plays a vital role. The surface exchange capacity in turn depends on the surface charge density and the particle geometry of each clay mineral. Thus the results of the experiments of Carlson et al. (1968) were explained as follows: (i)

Since kaolinite particles in the suspension were thick, the charge density on the small surfaces of these particles was high, possibly similar to that of montmorillonites. (ii) Illite particles, in contrast, were much finer than the other two minerals. For this reason, more cations were required per unit weight of clay to effect proper charge distribution for the cation bridge.

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(iii) Moreover, illite particles have a much higher negative charge on their surfaces than the other clay minerals. More cations per unit weight of clay would be needed to balance this higher negative surface charge, which is essential for the clay to form the clay–cation–virus bridge. On the other hand, Lipson and Stotzky (1983) plotted the adsorption of reovirus by clay minerals (mixed with cations) as a function of the surface area of kaolinite and montmorillonite, and reported that adsorption was not related to the surface area. They further asserted: (a) Adsorption was not related to the surface charge density of the clays, which they defined as the ‘CEC per specific surface’. (b) CEC of the clays is the most important factor involved in their adsorption mechanism. The above workers used the term surface area of clay minerals instead of specific surface area. But it is clear from their discussions that they actually meant the latter term, which is indeed more appropriate in this context. The unit of ‘surface area’ of kaolinite and montmorillonite is stated to be m2 /g (Lipson and Stotzky 1983, p. 677), i.e., area per unit mass, which is actually the unit of specific surface area. It is to be noted that the above contradictory views regarding the roles of specific surface area and surface charge density of clay minerals were based on the investigations carried out nearly 40–55 years ago. Further investigations are highly recommended to throw light on this subject, using the state-of-the-art instruments and research infrastructures that are made available by the technological progress over the last few decades.

2.1.6 Possible Effects of Other Physico-Chemical Properties of Clays on Their Virus Adsorption Mechanism Electrophoretic mobility is the solute’s response to the applied electric field in which cations move toward the negatively charged cathode, anions move toward the positively charged anode, and neutral substances remain stationary. Carlson et al. (1968) opined that the electrophoretic mobility of the clay particles was not related to the inactivation process, and thus they ruled out the possibility of inactivation of the virus by the clay minerals was caused by virus-to-clay electrical attraction. Carlson et al. (1968) further suggested that virus adsorption capacity of a clay mineral depends on its zeta potential in the solution, which is the potential difference between the clay particle surfaces and the bulk of the aquatic solution into which they are immersed (see Stern model, Sect. 2.4).

2.1 Clays Protecting from Viral Infections: The Mechanism of Virus Adoption

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2.1.7 Effects of Presence of Organic Matters The studies of Carlson et al. (1968) indicated that the presence of extraneous organic materials in a system considerably inhibited the process of virus adsorption. The natural organic particles such as proteins, lignin, and different types of carbohydrates could compete with the viruses for the adsorption sites on the clays, and reduced the number of sites available to the viruses. When present in sufficient quantities, the organic matters could also cause desorption of the viruses from the clay surfaces. Lipson and Stotzky (1984) studied the mechanisms through which some organic matters influenced the adsorption of reovirus to the surfaces of clay minerals. The organic matters selected for this study were three types of proteins, namely Ovalbumin, a-chymotrypsin, and lysozyme, and the clay minerals used were homoionic Na-kaolinite and Na-montmorillonite. They also investigated the effects of those proteins on the infectivity of the adsorbed reovirus. The inferences of this study are summarised below: (a) The adsorption of reovirus to both Na-kaolinite and Na-montmorillonite was significantly decreased by chymotrypsin and ovalbumin (b) Lysozyme reduced the adsorption of reovirus on Na-montmorillonite, but not on Na-kaolinite. (c) The proteins possibly competed with the virus for adsorption sites on the surfaces of Na-kaolinite and Na-montmorillonite. (d) The reduction in virus adsorption on the clay mineral surfaces was possibly related to either the molecular weight of the protein or the adsorption of each protein to cation-exchange sites on the clays. (e) In a distilled water medium without suspended clays, chymotrypsin and lysozyme decreased noticeably the infectivity of reovirus. But when these proteins were bound to montmorillonite, the infectivity of the virus was not much decreased. This indicated that the properties of the proteins that brought about the reduction of the infectivity of reovirus were altered at the clay-proteinvirus interface. It can therefore be inferred that in certain situations, the clay particles can remove the viruses from a system but preserve their infectivity.

2.1.8 Strength of Bonding Between the Clay Surfaces and the Adsorbed Viruses The viruses that are adsorbed on a clay particle adhere very strongly to the surface of the latter; and once adsorbed, they are not easily separated. The bonding of the viruses with the clay surfaces is stronger than that with most other substances. Few investigations have been carried out to explain this strong virus—clay bond. Block et al. (2016) applied transmission electron microscopy and biochemical methods to study the interaction between influenza virus and high-purity Na-montmorillonite. Some of their findings that are relevant to the present context are stated below.

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(i)

They found that the virus and the clay particles formed aggregates within 30 min of mixing, and most of the virus aggregated with clay while only trace amounts remained non-aggregated. (ii) They attributed the strong attraction of the virions to the montmorillonite faces to the hydrophobic interaction between them. (iii) The virus particles showed conspicuous morphological distortions (change of shape or form) after aggregation. While the mean projection area of the nonaggregated influenza virus was (8.0 ± 3.9) × 103 nm2 , that of the aggregated influenza virus was increased to (10.4 ± 6.1) × 103 nm2 . Such an increase in the projection area of the aggregated virus leads to an increase in their contact regions with the montmorillonite surfaces, which may contribute to the strong force of attraction in between them. (iv) In spite of the morphological changes, the structural integrity of the virions appeared to remain unchanged. For this reason, the viruses were still infectious after adsorption, though their infectivity level decreases substantially. This has already been explained in Sect. 2.1(b) of this chapter. In addition to the enhanced attractions between the viruses and clay surfaces by the morphological distortion of the former, it has been confirmed from some recent investigations that the clay minerals are more strongly attached to the spikes of enveloped viruses than the ACE2 proteins of humans and other animals (Abduljauwad et al. 2020). See Chap. 6, Sects. 6.3 and 6.4 for a detailed explanation on this subject.

2.2 Antibacterial Actions of Clay Minerals Natural clays can protect us from a wide range of pathogenic bacteria. But it is to be noted here that the mode of defensive actions of different types of clays against the same bacteria may vary considerably. Moreover, different antibacterial actions of the same clay mineral against different types of bacteria have also been observed. The protective actions of the natural clay minerals against bacterial infections may be categorised as follows: • The bactericidal actions involve the destruction of bacteria cells. • The bacteriostatic actions inhibit the growth of bacteria. • The adsorption of bacteria onto the edge and basal surfaces of clay minerals leads to their removal from a system. • Other antibacterial actions of clays, include resisting the bacteria by strengthening or recovery of the immune system of the host, removal of toxins secreted by the bacteria, etc. The subsequent part of this section provides a systematic account of the mechanisms involved in some of the important antibacterial actions of clays.

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2.2.1 The Mechanisms of Clay-Supported Bactericidal Processes (a) Differences between the natural antibacterial and non-antibacterial clays Some types of natural clays and their derivatives, especially those rich in smectites and illites, can destroy bacteria in vitro and also in vivo; while some other types are not much effective in this regard. The analysis of the mineral assemblages, chemical compositions and textures of different types of antibacterial clays (Cunningham et al. 2010; Williams et al. 2008, 2011) and comparing them with non-antibacterial clays help to identify the constituents and/or the properties that impart in the clays their bactericidal potentialities, which in turn may throw light to the mechanisms of the associated processes. The following differences between antibacterial and nonantibacterial clays have been identified by analysing the natural clays from different sources. (i)

Expandable clay minerals like smectite and illite, which expand in volume by incorporation of water or other substances in their interlayer spaces, are greater than 50% (wt.) in the antibacterial clays. The proportion of these clays is much less in the non-antibacterial clays. (ii) The average crystal diameter of the antibacterial clays ( 1, the proportional distribution of a toxin at higher concentrations is greater than that at lower concentrations. An isotherm (Greek isos: same/equal, therme: warmth/temperature) is measured at a constant temperature. The effect of temperature on the adsorption of toxins may not be very large, but still, it is significant, and depends mainly on the type of adsorption mechanism involved. The adsorption of some organic toxins, with little or no polarity, is controlled by their solubility in an aqueous medium. If temperature variation results in a substantial change in solubility, it may also bring about a conspicuous change in the adsorption. The solubility of relatively large organic molecules (such as anthracene) increases with an increase in temperature. These molecules, therefore, have an increasing tendency to remain in the aqueous solution at a higher temperature. As a result, their adsorption to the clay minerals (or other adsorbents) is expected to decrease with increasing temperature.

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5.2 Clay Minerals in the Treatment of Orally Ingested Toxic Substances (a) Pesticides and herbicides are the largest contributors to the external toxins that are ingested in the human body. Because of their high adsorptive capacity, clay minerals can protect the digestive mucosa against the damages caused by these toxins. A widely used herbicide, diquat dibromide [C12 H12 Br2 N2 ], can be retained in agricultural products; and when ingested in the human body, potentially causes severe physiological disorders. When swallowed, inhaled, or absorbed through the skin in sufficient quantities, this toxin may lead to fingernail discolouration (brown), gastrointestinal problems (like paralytic ileum), neuromuscular and skeletal disorders (like rhabdomyolysis), cataract, renal failure, proximal proteinuria, and even respiratory issues like pulmonary fibrosis. Theodorou et al. (1995) investigated the impacts of diquat on the intestinal permeability and the spinnability of gastrointestinal mucus of rats and found toxin-induced erosions of the intestinal mucosa and fluid hypersecretion in the animals under study. Their studies further revealed the effectiveness of diosmectite treatment (diosmectite < dioctahedral smectite. see Chap. 1, Sect. 1.3(ii) for a detailed discussion on its structure) in the prevention of the above disorders, which prompted them to infer that the treatment by diosmectite prevented functional alterations of the gastrointestinal mucosa, and also corrected the decrease of body weight in the rats induced by diquat. (b) Paraquat [(C6 H7 N)2 Cl2 ] is another common herbicide having a chemical composition similar to that of diquat, can be potentially harmful to human health, which may lead to pulmonary oedema, fibrosis, and in extreme cases, death due to multiple organ failure (Vale et al. 1987). The studies by Meredith and Vale (1987) indicate that the clay minerals smectite group, fuller’s earth (calcium montmorillonite) and bentonite (sodium montmorillonite), were effective adsorbents of paraquat that can be administered orally, and may be recommended for the treatment of poisoning caused by other chemical herbicides and pesticide. (c) Strychnine (C21 H22 N2 O2 ), which is widely used as pesticides particularly for killing small vertebrates such as birds and rodents, can be ingested by the human body through agricultural produces. It can severely affect the human nerve, by obstructing postsynaptic glycine receptors of the spinal cord that brings about painful, involuntary skeletal muscular disorders (Otter and D’Orazio 2020). The ability of some clay minerals to adsorb strychnine was established by Droy-Lefaix et al. (1986); and it was later corroborated by Schönsee et al. (2021) through their investigations on the sorption of a wide range of phytotoxin substances, including strychnine, by kaolinite and montmorillonite. The Freundlich sorption coefficients, expressed as log Dclay (in Litre per Kilogram), determined by Schönsee et al. (2021) were > 0.1 for kaolinite and > 0.5 for montmorillonite.

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(d) Among the common contaminants of foods that are synthesised externally by different microbes, the toxins of the mycotoxin group are very common. They are produced on different types of grains like wheat, oats or maize by various Fusarium species such as Fusarium graminearum, F. sporotrichioides, F. poae and F. equiseti. Trichothecene, a large subfamily of mycotoxins having the general chemical formula C15 H24 O (National Center for Biotechnology Information 2021a) may cause vomiting and lacerations of the gastrointestinal tract. Fioramonti et al. (1987b) established that some clays rich in smectite group minerals, such as bentonite, can protect humans and animals from these gastrointestinal disturbances, either by adsorption of this toxin from the food before its oral ingestion or by strengthening the gastric mucosa when applied before the contamination. (e) The T-2 toxin, a type of mycotoxin having the general formula C24 H34 O9 (National Center for Biotechnology Information 2021b) produced by the fungi Fusarium sporotrichioides and Fusarium poae in the cereal grains, causes alimentary toxic aleukia in humans, potentially leading to diarrhoea, haemorrhage, severe skin inflammation and even death. The studies of Fioramonti et al. (1987a) on the mice revealed that smectite (bentonite) could protect against T-2 induced disturbances of gastrointestinal transit. When bentonite is added to the food contaminated with T-2 toxin, its harmful effects were found to be significantly reduced, which the authors attributed to the capacity of smectites to bind T-2 in the gastrointestinal tract of the animals. (f) The toxins of the aflatoxin group are synthesised in the nuts, maize kernels, and dried fruits by the microbes Aspergillus flavus and A. parasiticus (Smith 1997). While ingested through those foods, these toxins may cause various injuries in hepatic tissues, including the destruction of centrilobular zones, thickening of central veins and cirrhosis (D’Mello 2020). A liver disease epidemic in large parts of India in 1974 was caused by aflatoxin contamination from the decaying grains (Krishnamachari et al. 1975). Schell et al. (1993) studied the effects of different types of clay minerals on animals suffering from aflatoxin contamination. They found that in most situations, the clay minerals could significantly reduce the health disorders, while Ca montmorillonite (fuller’s earth) and Na montmorillonite (bentonite) are more effective than palygorskite and sepiolite in this respect.

5.3 Clay Minerals in the Treatment of Toxic Substances Synthesised Within Human Body The toxins that are synthesised by various pathogens, mainly bacteria, in the body of humans and other animals can be categorised into the following two broad classes: (i) Endotoxins: They are also known as lipopolysaccharides (LPS), which are large molecules of relatively stable, heat tolerant lipid-polysaccharide complexes

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(Lipo < lipid: fat; poly: many; saccharide < sacchar: sugar). Many sugar molecules combine together to form a polysaccharide molecule. These toxins consist of O-antigen, with their outer core and inner core joined by a covalent bond. They are found in the outer membrane of Gram-negative bacteria and are liberated by cell lysis (destruction of the cell) after the death of bacteria (Murray 2016; Rietschel et al. 1994). (ii) Exotoxins: They are a group of soluble proteins. In contrast to the endotoxins, they are secreted by both Gram-negative and Gram-positive bacteria and catalyse the covalent modification of a host cell component(s) to alter its physiology (after Barbieri 2009). Enterotoxin is a group of protein exotoxins that specifically affect cells of the intestinal mucosa, causing vomiting and diarrhea, synthesized by different species of Bacillus, Clostridium, Escherichia, Staphylococcus, and Vibrio. They are heat labile (i.e., altered or decomposed at high temperature, approximately above 60 °C), soluble in water, and frequently cytotoxic (i.e., toxic to the cells). They can destroy the epithelial cells of the intestinal wall by altering their apical membrane permeability (after Dorland’s Medical Dictionary 2007; Gyles et al. 1974). The bacteria that causes cholera, Vibrio cholerae, produces an enterotoxin known as cholera toxin in human intestines. This inhibits absorption in the intestines and enhances intestinal secretion, leading to watery diarrhoea and profuse fluid loss. Another type of enterotoxin is synthesised within the human body by the Escherichia coli bacteria commonly found in contaminated water, which causes hemorrhagic colitis and haemolytic uremia syndrome. The anaerobic gram-positive microbe Clostridium perfringens type A (and in some cases by types C and D also), commonly found in meat, poultry, dairy products, fruits, vegetables, meat-based gravies, etc., can also synthesise several types of enterotoxin in the human ileum. These enterotoxins bind to intestinal epithelial cells and cause diarrhoeal syndromes in the patients, and may bring about long-lasting damages to the health by obstructing glucose transport and causing loss of protein (Leikin and Paloucek 2008). While studying the gastro-intestinal motility of dogs caused by the toxins produced by Vibrio cholerae, Fioramonti et al. (1987b) found that smectite treatment has an antidiarrhoeal effect that can counteract the digestive motor disturbances induced by experimental administration of those toxins. Later, the studies by Brouillard and Rateau (1989) confirmed that smectite and kaolin could adsorb the toxins of Vibrio cholerae and Escherichia coli by hydrogen bonding, preventing them from being fixed to the membrane receptors on the cells. They further found that smectite was more efficient than kaolin in this regard, and these clays were effective against the verotoxin of EHEC when the pH was acidic, but could not adsorb significantly ST toxin of ETEC. Studying the protective effect of smectite treatment, Pons et al. (1997) obtained similar results on the New Zealand rabbits suffering from severe damage to ileal loops, caused by the directly administered heat-stable E. coli toxin (ST).

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Martirosian et al. (1998) also established that the toxic effects of enterotoxins synthesised by Bacteroides fragilis and Clostridium difficile, administered to humans and rats, respectively, could be suppressed by smectite treatment. Concluding Remarks Over the last few decades, a large number of investigations have established the unparalleled capabilities of clay minerals to bind and remove a wide variety of toxic materials. The pharmaceutical industry has been fruitfully utilising these antitoxic properties of the natural clays and their synthetic products. This chapter has described the application of these detoxifying properties of the clay minerals in the protection of human health, thus fulfilling one of the major objectives of this book, and emphasises the necessity to explore the immense potentialities of the clay nanocomposites for the production of more effective detoxifying agents. Definitions and Brief Descriptions of the New Terms Used in this Chapter 1.

2.

3.

4.

5.

Abdominal Distension The excessive or abnormal expansion of the abdomen is caused by the accumulation of substances like intestinal gases or fluid. It is generally not an illness by itself, but a symptom of an underlying disease or dysfunction in the body. Patients suffering from abdominal distension have a feeling of fullness, nausea, pain, and abdominal cramping. In extreme cases, the patients may also suffer from shortness of breath due to the upward pressure on the diaphragm and lungs. Buruli Ulcer It is a chronic infectious disease that mainly affects the skin and sometimes bone, typically on the arms or legs, developing painless open wounds in the affected zones. It is caused by Mycobacterium ulcerans that produce the unique toxin mycolactone of the mycotoxin group (after WHO Newsroom 2021). Colitis The main part of the large intestine is the colon, which absorbs water and electrolytes from food that has remained undigested. The inflammation of the inner lining of the colon is known as colitis. Infection, loss of blood supply in the colon, inflammatory bowel disease and invasion of the colon wall with collagen (a protein found in connective tissues) or lymphocytes (a type of white blood cells) are all possible causes of an inflamed colon. Hemorrhagic colitis is abdominal cramps and bloody diarrhoea, without fever. It can be caused by toxins produced by the bacteria Escherichia coli. Diarrhoea Frequent defaecation of watery and unformed faeces is diarrhoea. The common causes of acute diarrhoea include intestinal infections and food poisoning. Digestive Tracts The digestive tract is the assemblage of organs in which the foods and liquids are ingested, digested, absorbed, and their undigested portions are rejected as faeces. These organs include the mouth, pharynx (throat), esophagus, stomach, small intestine, large intestine, rectum, and anus, all of which are joined in a

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6. 7.

8.

9. 10.

11.

12.

13.

14. 15. 16. 17.

18.

5 Antitoxic Applications of Clays in the Protection of Human Health

long, twisting tube from the mouth to the anus. (After Webster’s New World Medical Dictionary 2008) Duodenum: See Small Intestine Epithelial Cells The epithelial cells are the type of cells that covers the body surface (skin), blood vessels, urinary tract, and other organs. Fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue (after Wynn 2004). Fluid Hypersecretion Excessive secretion of fluids; hyper—Greek huper: over, beyond, above normal. Gastritis The condition that inflames the mucosa (the stomach lining), causing gastric pain, dyspepsia, bloating and nausea. Gastrointestinal Transit The passage of foods and liquids through the stomach, small intestine and large intestine are called gastrointestinal transit. It is crucial for digestion and absorption of nutrients and rejection of the undigested part through the rectum. Geophagy It is the intentional consumption of soil-like substances like clay, chalk, etc., found in some children and pregnant women, and many non-human animals including primate species (after Pebsworth et al. 2019; Young 2011). Haemolytic Uremia Uremia or uremic poisoning is the toxic condition caused by renal failure (ur: urine, -emia: blood condition). The kidney cannot function properly in this condition, and the waste materials normally secreted in the urine are retained in the blood. Haemolytic means pertaining to the destruction of red blood cells (after Ehlrich and Schroeder 2013). Haemolytic uremia is a condition caused by the E. coli bacterium that results in the destruction of platelets and red blood cells and kidney failure. Hemorrhagic Colitis: See Colitis Ileum: See Small Intestine Intestinal Permeability: See Small Intestine Irritable Bowel Syndrome (IBS) It is the functional intestinal disorder of the bowels and their nerves, caused by either abnormal contractions of the intestinal muscles or abnormally sensitive nerves in the intestines. IBS is characterised by chronic and recurrent abdominal pain, abdominal distension, mucus in stools, and irregular bowel habits, with alternating diarrhoea and constipation. Jejunum: See Small Intestine

References and Further Reading

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19. Mucosa The mucosa is the mucus membrane that lines the inner side of the digestive tract, from the mouth to the anus. In the mouth, stomach, and small intestine, the mucosa contains tiny glands that produce juices to help digest food. (After Webster’s New World Medical Dictionary 2008) 20. Gastrointestinal Mucus The mucus is present in the mucosa of the stomach and intestines. It protects the inner lining of the stomach and intestine from gastrointestinal secretions, like enzymes, acids, etc. 21. Pulmonary Oedema Oedema is the swelling of cells, tissues or cavities of the body due to abnormal accumulation of fluids. Pulmonary means related to lungs (Latin pulmo, pulmon: lung) Pulmonary oedema is thus the accumulation of excessive fluids in the tissues of the lungs (after Ehlrich and Schroeder 2013). 22. Small Intestine The small intestine is the coiled portion of the digestive tract, up to 20 feet in length, in between the stomach and the large intestine, where a portion of the food is digested and the major part of the nutrients are absorbed. It is called the small intestine because it is narrower than the large intestine. It is divided into three parts: the first part connected to the stomach is called the duodenum, the middle part is the jejunum, and the last part that is longest and connected to the large intestine is the ileum (after Ehlrich and Schroeder 2013).

References and Further Reading Adamis, Z. and M. Timar (1980). Investigations of the effects of quartz, aluminum silicates and colliery dusts on peritoneal macrophages in vitro. In: Brown, R.C., Gormley, I.P., Chamberlain, M., Davies, R. (Eds.). The in vitro effects of mineral dusts. London. Adekeye, D.K., Aremu, O.I., Fadunmade, E.O., Araromi, A.A., Odeniyi, I., Adedotun, I.S. and M.K. Ajenikoko (2020). Bioactivities, Biomedical and Pharmaceutical Applications of Raw and Functionalized Clay Minerals: A Review. Biomed J Sci & Tech Res, 30(5): 23714–23722. BJSTR. MS.ID.005008. Barbieri, J.T. (2009). In: Encyclopedia of Microbiology (Third Edition). Benhamou, P.H., Berlier, P., Longue, J. and C. Dupont (1995). Intestinal manifestation during antibiotics treatments in children: A prospective study. Gastroenterology 108, Abstract 273. Brouillard, M.Y. and J.G. Rateau (1989). Adsorption potency of 2 clays, smectite and kaolin on bacterial endotoxin. In vitro study in cell culture and on the intestine of newborn mice. Gastroente´rologie Clinique et Biologique, 13: 18–24. Brusseau, M.L. and J. Chorover (2019). Chapter 8 - Chemical Processes Affecting Contaminant Transport and Fate. In: Mark L. Brusseau, Ian L. Pepper, Charles P. Gerb a (Editors): Environmental and Pollution Science (Third Edition), Academic Press, pp. 113–130. ISBN 9780128147191. Carnoy, C., Muller Alouf, H., Mullet, C., Droy-Lefaix, M.T. and M. Simonet (2000). Oral infection of mice with superantigenic toxic producing Yersinia pseudotuberculosis. Effect of diosmectite. International Journal of Medical Microbiology, 290: 477–482.

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Chem Safety (2016). Soil Adsorption Coefficient (Kd Kf/Koc/Kfoc). http://www.chemsafetypro. com/Topics/CRA/Soil_Adsorption_Coefficient_Kd_Koc.html#:~:text=Soil%20adsorption% 20coefficient%20(Kd)%20measures,water%20distribution%20coefficients%20(Kf).&text=Val ues%20for%20Kd%20vary%20greatly,not%20considered%20in%20the%20equation. Last visited: December 18, 2021. Choy, J.H., Kwak, S.Y., Park, J.S., Jeong, Y.J. and J. Portier (1999). Intercalative nanohybrids of nucleoside monophosphates and DNA in layered metal hydroxide. Journal of the American Chemical Society, 121(6): 1399–1400. D’Mello, J.P.F. (Ed.). (2020). A Handbook of Environmental Toxicology: Human Disorders and Ecotoxicology. CAB International. Dorland’s Medical Dictionary (2007). Elsevier. Droy-Lefaix, M.T., Schatz, B. and Y. Drouet (1986). Importance of viscoelasticity in the study of the adherent mucus gel. Digestive Disease Science, 31, Abstract 1401. Ehlrich, A. and C.L. Schroeder (2013). Medical terminology for health professions, 7th Ed. Delmar, Cengage Learning. Fioramonti, J., Bouaouiche, F., Droy-Lefaix, M.T., Plique, O., Corthier, G. and L. Bueno (1994). Diosmectite treatment delays colonic water secretion and reduces increase in intestinal permeability by Clostridium difficile toxins in rats. Gut, 35(Suppl 4): A31–A32. Fioramonti, J., Droy-Lefaix, M.T. and L. Bueno (1987a). Changes in gastric-intestinal motility induced by cholera toxin and experimental osmotic diarrhoea in dogs: Effects of treatment with an argillaceous compound. Digestion, 36: 230–237. Fioramonti, J., Fargeas, M.J. and L. Bueno (1987b). Action of T-2 toxin on gastrointestinal transit in mice: Protective effect of an argillaceous compound. Toxicology Letters, 36: 227–232. Fioramonti, J., Navetat, H., Droy-Lefaix, M.T., More´, J. and L. Bueno (1990). Antidiarrheal properties of clay minerals: Pharmacological and clinical studies. In: Simon, F., Lees, P., Semjen, G. (Eds.), Veterinary Pharmacology, Toxicology and Therapy in Food Producing Animals. Proceedings of the 4th Congress of Pharmacology and Toxicology, Budapest, 1988. University of Veterinary Science, Budapest, pp. 245–251. Gyles, C., So, M. and S. Falkow (1974). The enterotoxin plasmids of Escherichia coli. Journal of Infectious Diseases, 130(1): 40–49. Krishnamachari, K.A., Nagarajan, V., Bhat, R.V. and T.B.G. Tilak (1975). Hepatitis due to aflatoxicosis: An outbreak in Western India. The Lancet, 305: 1061–1063. Kim M.H., Park, D.H., Yang, J.H., Choy, Y.B. and J.H. Choy (2013). Drug-inorganic-polymer nanohybrid for transdermal delivery. International Journal of Pharmaceutics, 444(1-2): 120–127. Leikin, J.B. and F.P. Paloucek (2008). Poisoning and Toxicology Handbook, 4th Edition. Informa Healthcare USA, Inc. Lipson, S.M. and G. Stotzky (1983). Adsorption of reovirus to clay minerals: Effects of cationexchange capacity, cation saturation, and surface area. Applied and Environmental Microbiology, 46(3): 673–682. Lukas, K. and M. Lukas (2000). Dioctahedral smectite in the treatment of irritable colon. Prakticky Lekar, 80: 27–29. Madkour, A.A., Madina, E.M.H., El Azzouni, O.E.Z., Amor, M.A., El Waliti, T.M.K. and T. Abbass (1993). Smectite in acute diarrhea in children: A double-blind study placebo controlled clinical trial. Journal of Pediatric Gastroenterology and Nutrition, 17: 176–181. Mahaney, W.C., Hancock, R.G.V., Aufreiter, S. and M.A. Huffman (1996). Geochemistry and clay mineralogy of termite mound soil and the role of geography in chimpanzees of the Mahale Mountains, Tanzania. Primates, 37(2): 121–134. Martirosian, G., Rouyan, G., Zalewski, T. and M.F.Meisel (1998). Dioctahedral smectite neutralization activity of Clostridium difficile and Bacteroides fragilis toxins in vitro. Acta Microbiologica Polonica, 47: 171–183. Mastroianni, A., Canallieri, C., Coronado, O., Manfred, R., Chiodo, F. and S. Pignatari (1998). Smectite in AIDS-associated chronic idiopathic diarrheas. Minerva Gastroenterologica et Dietologica, 44: 231–234.

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Meredith, T.J. and J.A. Vale (1987). Treatment of paraquat poisoning in man. Methods to prevent absorption. Human Toxicology, 6: 49–55. Murray L., Little, M., Ovidiu, P. and K. Hoggett (2015). Toxicology Handbook, 3rd Edition. Elsevier Australia. Murray, P.R. (2016). Medical Microbiology. Eighth edition. India: Elsevier Inc. National Center for Biotechnology Information (2021a). PubChem Compound Summary for CID 104763, Trichothecene. Retrieved September 20, 2021a from https://pubchem.ncbi.nlm.nih.gov/ compound/Trichothecene. National Center for Biotechnology Information (2021b). PubChem Compound Summary for CID 5284461, T-2 Toxin. Retrieved September 20, 2021b from https://pubchem.ncbi.nlm.nih.gov/ compound/T-2-Toxin. Neitzel, I., Mochalin, V. and Y. Gogotsi (2012). Chapter 13 - Advances in Surface Chemistry of Nanodiamond and Nanodiamond–Polymer Composites. In: Shenderova, O.A., Gruen, D.M. (Eds). Ultananocrystalline Diamond (Second Edition), William Andrew Publishing, pp. 421–456. ISBN 9781437734652. https://doi.org/10.1016/B978-1-4377-3465-2.00013-X. Otter, J. and J.L. D’Orazio (2020). Strychnine toxicity. Stat Pearls Publishing. PMID: 29083795. Bookshelf ID: https://doi.org/NBK459306. Opriu, A.L., Diculescu, M., Lov, A., Calin, S., Dumitrescu, A., Calin, G., Manuc, M. and D. Pitigoi (1996). Enterocyte covering agent versus intestinal motility inhibition in the irritable bowel. Gut 9, Abstract 34. Pebsworth, Paula A., Huffman, M.A., Lambert, J.E. and S.L. Young (2019). Geophagy among nonhuman primates: A systematic review of current knowledge and suggestions for future directions. American Journal of Physical Anthropology, 168 (S67): 164–194. https://doi.org/10.1002/ ajpa.23724. Perrotin, D., Legras, A., Boulain, T. and G. Ginies (1990). Diarrhea under parenteral nutrition in reanimation. Prevention study using an adsorbent drug. In: Re´animation et Appareil digestif. Socie´ te´ de Re´animation de Langue franc- aise, Paris, pp. 49–53. Phillips, T.D. (1999). Dietary clay in the chemoprevention of aflatoxin-induced disease. Toxicological Sciences, 52(Suppl 1): 118–126. Pons, L., Droy-Lefaix, M.T., Leguere, N. and J. Guillemain (1997). Protective effects of diosmectite from alterations of mucosal permeability and morphology of rabbit ileal loops induced by Escherichia coli enterotoxin. Gastroenterology 112, Abstract 395. Rietschel, E.T., Kirikae, T., Schade, F.U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A.J., Zähringer, U., Seydel, U. and F. Di Padova (1994). Bacterial endotoxin: Molecular relationships of structure to activity and function. FASEB J., 8(2): 217–225. https://doi.org/10.1096/fasebj.8. 2.8119492. Santantonio, M., Colella, M., Fiorica, F., Aratisali, S., Stefanelli, A. and A.M. Falchi (2000). Diosmectite (diosmectal) prevention antidiarrheic therapy in patients submitted to pelvic radiation. Minerva Gastroenterologica et Dietologica, 46: 225–230. Schell, T., Lindemann, M.D., Kornegay, E.T., Blodgett, D.L. and J.A. Doerr (1993). Effectiveness of different types of clay for reducing the detrimental effects of aflatoxin- contaminated diets on performance and serum profiles of weanling pigs. Journal of Animal Science, 71: 1226–1231. Schönsee, C.D., Wettstein, F.E. and T.D. Bucheli (2021). Phytoxin sorption to clay minerals. Environmental Sciences Europe, 33: 36. https://doi.org/10.1186/s12302-021-00469-z. Secondulfo, M., Mennella, R. and C. Fenderico (2002). Ruolo dei fattori psicologi nei pazienti affeitti da sindrome dell’intestino irritabile. Internista, 10: 169–173. Smith, J.E. (1997). Aflatoxins. In: D’Mello, J.P.F. (Ed.). Handbook of Plant and Fungal Toxins, 1st edn. CRC Press, Boca Raton, Florida, pp. 269–285. Theodorou, V., Chrestian, B., Fioramonti, J., Droy-Lefaix, M.T. and L. Bueno (1995). Diosmectite treatment prevents intestinal permeability and mucus alterations induced by ingestion of a pesticide in rats. Gut 37, Abstract 148. Vale, J.A., Meredith, T.J. and B.M. Buckley (1987). Paraquat poisoning: clinical features and immediate general management. Human Toxicology, 6: 41–47.

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Webster’s New World™ Medical Dictionary, Third Edition (2008). World Health Organization Newsroom (2021). Buruli ulcer. https://www.who.int/news-room/factsheets/detail/buruli-ulcer-(mycobacterium-ulcerans-infection). Last updated: 17 May 2021. Last visited: 22 September 2021. Wynn, T.A. (2004). Fibrotic disease and the TH1/TH2 paradigm. Nature Reviews. Immunology. Springer Science and Business Media LLC, 4(8): 583–594. https://doi.org/10.1038/nri1412. ISSN 1474-1733. Young, Sera L. (2011). Craving Earth: Understanding Pica: The Urge to Eat Clay, Starch, Ice, and Chalk. New York: Columbia University Press.

Chapter 6

Clays in the Global War Against COVID-19: Why are They Preferable Over the Conventional Weaponry?

Introduction The Coronavirus Disease 2019, better known as COVID-19, needs no introduction to the readers around the world today. This highly contagious disease, caused by the SARS-CoV-2 virus, can spread over a large population with unprecedented rapidity; causing potentially fatal health disorders with no definite treatments. It has also brought about long-lasting damages to the economy of many countries by prolonged lockdowns, thus leading to a global catastrophe that is continuing to date. Towards the end of 2021 when this study was being been drafted, majority of in the world population was observed to have been directly or indirectly affected by this catastrophe; on a personal note, the contributors towards this study have seen the severe afflictions and even untimely demise of some of their near and dear ones by this disease. Considering the unusually high spreading rate of this disease, the inability of the conventional medical treatments to cure it, the rapidity of the emergence of the new variants of its pathogen, and looking at the harmful effects of the conventional sanitisers and disinfectants, it is unquestionably the need of the hour to explore all possible means to find some alternative ways for its prevention and cure. The clay minerals show enough potential to provide new, unconventional ways to fight this menace. Conforming to the objective of this book, the multifaceted applications of clays in the treatment of some common diseases caused by microbes and toxins have been discussed in Chaps. 4 and 5, respectively. But such a discourse is not complete unless we conclude it with this chapter, which gives an overview of the prospective applications of clays for the prevention and cure of COVID-19. Section 6.1 briefly describes the essential features of the pathogen SARS-CoV-2 and its effects on human health. Section 6.2 explains the adverse effects of soaps, detergents, and alcoholbased sanitisers on human health and the environment. The suggested or proven applications of clays in the prevention of the propagation of this virus have been described in Sect. 6.3. Finally, Sect. 6.4 discusses the prospective applications of clays and their derivatives in the treatment of COVID-19. © Capital Publishing Company, New Delhi, India 2023 B. Ghosh and D. Chakraborty, Clay Minerals, https://doi.org/10.1007/978-3-031-22327-3_6

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6.1 Characteristic Features of SARS-CoV-2 Viruses, the most abundant organisms on the Earth, are very small, submicroscopic pathogens consisting of a nucleic acid molecule surrounded by a protein covering, which are able to multiply only within living cells of a host, and behave as a non-living being outside a living cell (Breitbart and Rohwer 2005; Suttle 2005). Most viruses are not visible under common optical microscopes, except the largest and most complex ones. Electron microscopes are required to study them. Their size ranges from 20 nm (1 nm = 10–9 m) to ~250–400 nm in diameter, the largest ones having lengths of upto 700–1000 nm. (https://www.britannica.com/science/virus/ Viral-DNA-integration). Viral nucleic acids can be Ribonucleic Acid (RNA) or Deoxyribonucleic Acid (DNA), double-stranded (ds) or single-stranded (ss), and linear or circular. In addition, RNA of the viruses are of two categories: positive or ‘sense’ strand (coded information about how to build proteins); and negative or ‘antisense’ strand. Some viruses are enveloped by lipid membranes (envelope or peplos), which are called enveloped viruses, and those lacking the lipid membranes are called nonenveloped viruses. The envelopes of some viruses may be covered with spikes, which are large cone-shaped structures projecting out from the surface of the envelope. These spikes are composed of a special type of protein called glycoprotein or peplomer protein, which contains oligosaccharide chains (glycans) covalently attached to amino acid side-chains (Burrell 2006). The viruses are classified into a large number of divisions and subdivisions based on all the diversified characters of their nucleic acids, protein shells, presence or absence of envelopes, etc. Coronaviruses form a diverse group of viruses belonging to the order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae, and can infect humans, bats, bovines, camels, cats, etc. (Cascella et al. 2021). These viruses can cross the species barriers, i.e., can be transmitted from one species to another. Two highly infectious coronaviruses, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) appeared in 2002 and 2012, respectively, which caused fatal respiratory illness to a large number of individuals. The acronym SARS-CoV-2 stands for a newly introduced type of coronavirus, named the Severe Acute Respiratory Syndrome Coronavirus 2, which was first reported from the city of Wuhan, China at the end of 2019. All these coronaviruses are enveloped, positive-stranded, singlestranded RNA (+ssRNA) viruses, having their envelopes covered with numerous protein spikes (Fig. 6.1). Due to the presence of these spikes, they have a crownlike appearance as visible under an electron microscope, and coronam being the Latin term for the crown, they are named coronaviruses. The spikes are coated with polysaccharide molecules, which help to camouflage them and allow them to evade the host immune system during entry (Watanabe et al. 2020). The SARS-CoV-2 is round or elliptical in shape, and has a diameter of approximately 60–140 nm. This is often found to be pleomorphic, i.e., different individuals of the same species may have different shapes, sizes and other characteristics. It is

6.1 Characteristic Features of SARS-CoV-2

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Fig. 6.1 Schematic diagram of the SARS-CoV-2 virus, and the components

sensitive to UV rays and high temperatures and can be inactivated by lipid solvents like ether, ethanol, strong alkalis, etc. (Cascella et al. 2021). A comprehensive description of the spike of SARS-CoV-2 has been given by Huang et al. (2020a, b). Each spike (S) is divided into two subunits, S1 and S2 (Fig. 6.1). When the virus targets a host cell, a receptor-binding domain of S1 recognises some receptor molecules situated on the cell membrane of that cell and binds to them (see Sect. 6.1.3 for further discussion). Thus the virus is attached to the host cell. Two heptapeptide repeat sequences of S2, known as HR1 and HR2 (Fig. 6.1), then cause fusion of the host cell membrane, to enable the entry of the virus into the host cell.

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6.1.1 Common Variants of SARS-CoV-2 SARS-CoV-2, like the other RNA viruses, is capable of undergoing rapid genetic evolution. Within a short time span, a number of new mutant variants of this virus can be introduced, which are different from the ancestral strains. This highly contagious virus emerged in Wuhan, Hubei Province, China in December 2019 (Huang et al. 2020a, b). Four mutant variants of this virus appeared within one year (Table 6.1), which were designated as variants of concern (VOC) by the WHO’s Technical Advisory Group on Virus Evolution (TAG-VE). During the finalisation of this book, the authors came across the discovery of a new variant named Omicron appeared in November 2021 (Table 6.1), which was also designated as a VOC. Other than WHO, these variants have been declared as VOC by many reputed national and international health organisations as well, such as the Centers for Disease Control and Prevention (CDC) of the USA, Public Health England (PHE), the COVID-19 Genomics UK Consortium for the UK, and the Canadian COVID Genomics Network (CanCOGeN). All these variants of concern satisfy one or more of the following criteria (after CDC 2021; WHO 2022): (i) (ii) (iii) (iv) (v)

Increase in transmissibility, i.e., ability to spread more quickly in people. Detrimental change in COVID-19 epidemiology (incidence, distribution, and possible control). Increase in virulence, i.e., ability to cause more severe disease or an increased risk of death compared to other variants. Change in clinical disease presentation. Decrease in the effectiveness of public health and social measures.

Table 6.1 The dates of earliest detection of the common variants of concern of the SARS-CoV-2 Name

Earliest detection

Alpha (B.1.1.7)

Earliest detected on 20th September 2020 in the United Kingdom (UK) from a sample collected on 3rd September 2020 [1], this variant spread very quickly in Mid-December 2020

Beta (B.1.351)

First reported from South Africa on 8th October 2020 [2]

Gamma (P.1)

First detected in Brazil on 15th December 2020 [3]

Delta (B.1.617.2)

First reported from India on 3rd November 2020, the earliest sample date being 11th September 2020 [4].

Omicron (B.1.1.529)

First reported to WHO from South Africa on 24th November 2021 [5], [6]

Web References: [1] https://cov-lineages.org/global_report_B.1.1.7.html, [2] https://cov-lineages.org/global_report_B.1.351.html [3] https://cov-lineages.org/global_report_P.1.html [4] https://cov-lineages.org/global_report_B.1.617.2.html [5] https://www.who.int/news/item/28-11-2021-update-on-omicron [6] https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov2-variant-of-concern

6.1 Characteristic Features of SARS-CoV-2

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(vi)

Decrease in the effectiveness of the available diagnostics—ability to evade detection by specific viral diagnostic tests. (vii) Decrease in the effectiveness of the available vaccines—greater ability to evade the immunity acquired naturally or through vaccination. (viii) Decrease in the effectiveness of the available medications, and decreased vulnerability to therapeutic agents like monoclonal antibodies (laboratorymade proteins that imitate the immune system’s ability to repel pathogens such as viruses)

6.1.2 Entry of SARS-CoV-2 in Human Cells: The Role of hACE2 The angiotensin-converting-enzyme 2 present on the cell membrane of humans is connected to the SARS-CoV-2 and enables the virus to enter into a human cell, as shown schematically in Fig. 6.2. A brief explanation of this process is given below. The class of enzymes in which metal ions are bound to the protein molecules is called metalloenzymes. The human angiotensin-converting enzyme 2 or hACE2 is a zinc-containing metalloenzyme, which is attached to the cell membranes of many organs of the human body (Fig. 6.2a), including the upper respiratory tract, lungs, intestinal enterocytes, renal tubular cells of the kidney, gall bladder, heart, etc. This enzyme has wide-ranging physiological activities and can resist the harmful actions of the renin-angiotensin system in many diseases (Hikmet et al. 2020; Turner 2015; Wrapp et al. 2020 may be consulted for detailed descriptions of this enzyme). Being a transmembrane protein, hACE2 acts as the cell entry receptor for the entry of the SARS-CoV-2 in the human body. The spike on the surface of the SARS-CoV-2 has a high affinity to hACE2 and binds strongly to it on the surface of cells (Callaway and Spencer 2020; Li 2003; Li et al. 2005; Xu et al. 2020). As stated in Sect. 6.1.1, the spike proteins of SARS-CoV-2 are composed of two subunits, S1 and S2. The receptor-binding domain of S1 binds with hACE2 of the host cells (Fig. 6.2b and c). De Andrade et al. (2020) studied the binding protein complexes involving the receptor-binding domains from these two viruses with the hACE2 by computer simulation. Their studies indicated that the chemical affinity of SARS-CoV-2 for the hACE2 enzyme virus is much higher than that of SARSCoV (of 2002). The results of this computer simulation have been corroborated by Wrapp et al. (2020), who showed that the binding affinity between SARS-CoV-2 spike glycoprotein and hACE2 is 10- fold to 20-fold higher than that between SARSCoV and hACE2. Zhou et al. (2020) further established that SARS-CoV-2 can only enter into the cells containing ACE2, and not in the cells without ACE2. This virus cannot even penetrate into the cells containing the cell receptors for the other types of coronavirus, such as aminopeptidase N and dipeptidyl peptidase 4.

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Fig. 6.2 Schematic diagram showing the entry of coronavirus into a human cell. a Host human cell has hACE2 enzyme molecules on its membrane. b Virus spike protein is attached to the hACE2. c Magnified view of the zone bounded by red dashes in b, showing the attachment of receptor binding domain of S1 with hACE2. d Entry of the virus into the host human cell. [Graphic works by the authors]

After binding, both the hACE2 and the virus enter into the target human cells (Fig. 6.2D). For further elaborations regarding the structure and functions of SARSCoV-2 spike protein and its interactions with the hACE2, Huang et al. (2020a, b), Millet and Whittaker (2018), and the review by Ni et al. (2020) may be consulted.

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97

6.1.3 Effects of SARS-CoV-2 on Human Health In the respiratory system, hACE2 is abundantly present on the epithelial cells of the alveolus, but it is much less common on the epithelium of oral and nasal mucosa and nasopharynx. The lungs are therefore primarily affected by SARS-CoV-2. This virus can also affect the other vital organs like the heart, small intestines and kidneys since hACE2 is also present in considerable amounts on the myocardial cells, enterocytes of the ileum, and the proximal tubular cells of the nephrons. Together with severe damages in the lungs, critically ill patients suffering in COVID-19 may therefore develop multiple organ damage, including acute kidney injury, cardiac issues, dysfunction of the liver, etc. (Hamming et al. 2004; Ni et al. 2020; Yang et al. 2020; Zou et al. 2020). The injurious effects of this virus on different organ systems are briefly described here. (a) Effects on the respiratory and vascular system: Since the SARS-CoV-2 primarily targets the respiratory and vascular systems, pneumonia and other respiratory and vascular diseases are most commonly observed in the infected persons. In the early stage of the pneumonia, the virus replicates rapidly in the host cells, bringing about virus-mediated tissue damage. In the later stage, the infected host cells activate an immune response. In severe cases, the immune system is over activated and releases very high levels of cytokines into the circulation. Cytokines are a broad category of proteins that are important in cell signalling, and essential for the immune responses of the body against infections (Dinarello 2000). They assist in cell to cell communication during immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma (Mandal 2020). However, excessive secretion of cytokines, known as cytokine storm, can result in a dangerous systemic inflammatory response syndrome and multi-organ failure, which may even lead to the death of the infected individuals. In many cases, cytokine storms are considered as the cause of increased vascular permeability, pulmonary edema, extensive lung tissue damage and dysfunctional coagulation in a large number of COVID-19 patients, ultimately leading to their death (Azkur et al. 2020; Cron et al. 2020; Mehta et al. 2020; Ruan et al. 2020; Wang et al. 2020). (b) Effects on the nervous systems: Although the respiratory system is the main target for SARS-CoV-2, this virus has also been reported to cause severe neurologic disorder in humans by attacking the central nervous system (CNS). Entering the human CNS through the olfactory-hematogenous pathway, it can degenerate the nerve cells, leading to loss of olfactory functions and severe ischemic stroke (Bergmann et al. 2006; Iroegbu et al. 2020). (c) Effects on the cardiovascular system: The hACE2 receptors present in the cells of the heart muscle (myocardial cells) are attached to the SARS-CoV-2 viruses, to cause inflammation of the heart muscles known as myocarditis (Cascella et al. 2021). Excessive release of proinflammatory cytokines (i.e., the cytokines capable of promoting inflammation) can also lead to vascular inflammation,

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myocarditis, and cardiac arrhythmias (Huang et al. 2020a, b). Acute coronary syndrome (ACS) can be caused by COVID-19 associated with excessive release of proinflammatory cytokines, and worsening of pre-existing coronary artery disease (Hua et al. 2020; Guo et al. 2020). (d) Effects on the other systems: The other major organ systems affected by this virus are the gastrointestinal tract (Patel et al. 2020), the hepatobiliary system (Aleem and Shah 2021), and the renal system (Gabarre et al. 2020; Ziemba et al. 2021).

6.2 Prevention of Covid-19: Common Practices and Associated Problems The SARS-CoV-2, being highly infectious, can be transmitted over a large population within a short time. Several investigations have been carried out so far for understanding the modes of transmission of this virus. Such laboratory studies are generally performed on transgenic animals, which are created by deliberately inserting a gene into the genome of an animal, commonly mice (Shankar and Mehendale 2014). For the coronavirus research, McCray et al. (2007) developed a hACE2 transgenic mouse strain successfully by the introduction of a vector carrying hACE2-coding sequence into wild-type mice long before the outbreak of COVID-19 pandemic (Wang 2020). Simulating different modes of virus transmission in the laboratory, it has been established that the virus can be transmitted readily among the hACE2-transgenic mice by close contact. The liquid droplets released from the nose or mouth of an infected individual through respiration, coughing, or sneezing is considered to be the major cause of spreading the virus, especially in a closed and poorly ventilated environment (Bao et al. 2020; Wang et al. 2005). The common remedial measures for prevention of the transmission of liquid droplets from one person to another are given below. (a) Prevention of airborne transmission: Oral and nasal discharges of the infected individuals, containing this virus in substantial amounts, may be transported by air to some distance. Covering the nose and mouth with appropriate masks, and maintaining a physical distance of 2 m can effectively protect from airborne transmission of this virus. (b) Prevention of spreading via hand to hand contact: This virus may be transmitted very easily by touching the hand of an infected individual. Frequent sanitisations of hands are essential for preventing infection spread through hand to hand contact. Alkaline soaps, especially the liquid varieties, and alcohol-based hand sanitisers are commonly used to disinfect the hands. (c) Prevention of infection by surface to skin contact: This virus can survive for several hours on the surfaces of a wide variety of common materials, and can therefore be readily transmitted by the contact of such a contaminated surface with human skin. Detergents and alcohol-based sprays are the most widely used surface sanitisers.

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It is clear from the above discussion that the importance of hand sanitisers and surface disinfectants cannot be overemphasized in the prevention of COVID-19. As a result, the demands for liquid soaps, detergents, and alcohol-based sanitizers increased manifold after the outbreak of this disease. This led to an unprecedented increase in their productions also. The production of alcohol-based sanitisers, for example, increased 600 times in 2020 (Abuga and Nyamweya 2021; Hoang et al. 2021). But all the conventional sanitisers mentioned above, although capable of preventing viral infections, have their own disadvantages, as shown in Figs. 6.3, 6.4 and 6.5. This has been explained in detail in the next three subsections.

Fig. 6.3 Adverse effects of alkaline soaps on human skin. See Sect. 6.2.1for detailed discussion. [Graphic works by the authors]

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Fig. 6.4 Effects of alcohol-based sanitisers and sprays on human health. See Sect. 6.2.2 for detailed discussion. [Graphic works by the authors]

6.2.1 Effects of Soaps on Human Skin Chemically, the toilet soaps are considered as sodium or potassium salts of fatty acids, produced by the reaction between the fatty acids (derived from oil or fat) and alkalies, like sodium hydroxide or potassium hydroxide. Hard soap cakes are produced from NaOH, while KOH is used to produce liquid soap hand washes. Frequent use of soaps may cause significant damage to the skin (Fig. 6.3). Normal, healthy human skin is slightly acidic, having a pH of ~ 5.5. It is protected by an acid mantle, a thin, acidic film on the skin’s surface composed of lipids and amino acids from the oil and sweat. But the alkali-based soaps have a high pH, mostly 9.01– 10, which may also be as high as 11 in some varieties (Tarun et al. 2014). The soap

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Fig. 6.5 Effects of detergents on human health and environment. See Sect. 6.2.3 for detailed discussion. [Graphic works by the authors]

residues adhering to the skin are attached to the skin’s lipid matrix, having prolonged effects after each wash. Repeated hand washing by soaps thus brings about increase in the skin pH, damage of the protective acid mantle, and lead to the following health issues: (i) (ii) (iii)

(iv)

(v)

This can cause dehydration of the skin and irritability, resulting in the dryness of skin, squamous skin, itching, irritation, and inflammation. Disruption of the activities of enzymes in the upper epidermis and change the condition of bacteria on the skin has also been reported (Gfatter et al. 1997). Increase of skin pH bring about rapid growth of the population of Propionibacterium is a genus of bacteria that causes long term skin infections like acne vulgaris (Baranda et al. 2002; Korting et al. 1987; Prakash et al. 2017). The skin is the habitat of a varied population of microorganisms, most of which are harmless or even beneficial to their host. Soap is one of the potential factors that have effects on these skin microbiota (Grice and Segre 2011). Damage of the acid mantle can significantly deteriorate the conditions of patients already suffering from skin diseases like acne, eczema, dermatitis, and rosacea (Pahr 2018).

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6.2.2 Effects of Alcohol-based Sanitisers and Surface Sprays on Human Health For the last couple of decades, alcohol-based hand sanitisers (ABHS) have been widely recommended for hand hygiene of medical professionals and common people alike. Ethanol and other alcohols, like n-propanol, isopropanol, aminomethylpropanol, benzyl alcohol, Phenoxyethanol etc. are the chief ingredients of the ABHS. More than half of the commonly used ABHS have two different types of alcohols; one third of them are composed of a single alcohol, and the remaining ones have three or four types of alcohols in them (see Table 2 of Bessonneau et al. 2010 for details). All these alcohols can effectively destroy a wide range of Gram-positive and Gramnegative bacteria, enveloped and non-enveloped viruses, and fungi (Boyce 2000). Furthermore, there are certain advantages of alcohol-based sanitizers over alkalibased antiseptic soaps. In addition to all the soap-induced skin issues described in Sect. 6.2.1, frequent handwashing with soaps require continuous water supply, access to a sink, and longer time for the hand washing procedure. The ABHS are therefore widely recommended for hand hygiene, especially for the healthcare professionals, in the guidelines published by the Centres of Disease Control and Prevention of U.S.A. and other similar organisations (Boyce 2000; Boyce and Pittet 2002; Bessonneau et al. 2010; Voss and Widmer 1997). Since the outbreak of the COVID-19 pandemic in the late 2019, the use of ABHS increased manifold for preventing hand to hand transmission of the SARS-CoV2. Also the alcohol-based sprays are considered as the most effective measure for surface disinfection. The hand sanitisers contain on average 70% by weight of one or more alcohols. The alcohol content in the sprays, on the other hand, may vary from 30% (Alhmidi et al. 2017) to 95% (Kampf 2004). Being a highly volatile matter, a substantial amount of alcohol is vapourised and spread in the surrounding air during each hand sensitisation procedure. The aerial dispersion of alcohols can be even greater during the application of alcohol-based sprays on any surface, which causes the release of larger amount of alcohol vapours, along with the suspension and floating of concentrated alcoholic aerosols in the surrounding air. This alcohol vapour enters into the alveolar spaces of the users through inhalation. Bessonneau and Thomas (2012) reported that after 90 s of hand disinfection, the total amount of inhaled ethanol may be as high as 328.9 mg. The quantity of inhaled alcohol is possibly greater than that after application of alcohol-based surface sprays, although no study in this regard has been seen so far. A large portion of this inhaled vapour is diffused from the pulmonary gases to the blood stream in the lungs, and the remaining part is exhaled. In addition, frequent application of ABHS on the skin of hands may increase the alcohol intake significantly. Though the dermal absorption of ethanol is negligible (~1%), human skin can absorb the other types of alcohols in substantial quantities (Institut National de Recherche et de Sécurité 2007).

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All these unintentional alcohol intakes, if continued for a long time, may lead to a number of serious health issues (Fig. 6.4), as listed below (after Bessonneau et al. 2010; MacLean et al. 2017; Tonini et al. 2009). (i)

(ii) (iii)

(iv) (v) (vi)

(vii)

Airborne alcohol vapour causes irritation of eye, nose, and throat; and can damage the mucus membrane. Alcohol-based surface sprays are particularly harmful in this regard. The alcohols ingested through lungs or skin is diffused all over the human body, and is transported rapidly to the brain, liver, kidney and other vital organs. When inhaled in large quantities, alcohols may affect the central nervous system, causing dizziness, nausea, hypotension (abnormally low blood pressure), and hypothermia (abnormally low body temperature). Prolonged exposures to isopropyl alcohol can cause irritations of the respiratory system. If ingested in larger quantity, isopropyl alcohol may also cause vocal cord dysfunction. Bessonneau et al. (2010) classified the detrimental effects of alcohols into three categories: intoxication, dependence and biochemical effects, and reported that ABHS-induced unintentional alcohol intakes are related to the biochemical effects, that can potentially deteriorate the condition of people suffering from hypertension and other cardiovascular diseases. People already having alcohol use disorder may be adversely affected by unintentional alcohol intakes: they are in the risk of suffering in psychosomatic issues pertaining to greater craving for alcohol (MacLean et al. 2017). The increased craving may even lead to further use or excessive indulgence of alcohol in some individuals, which may be seriously detrimental to their health.

6.2.3 Effects of Detergents on Human Health and Environment A substance that lowers the surface tension of the medium in which it is dissolved is known as a surfactant. Detergent is defined as a surfactant (or a mixture containing one or more surfactants) having cleaning properties in dilute solutions (IUPAC 1997). There are different classes of detergents with widely varying compositions, including the anionic detergents based on alkylbenzene sulfonates, cationic detergents containing quaternary ammonium cations, non-ionic detergents produced from polyoxyethylene or glycosides, and the amphoteric detergents consisting of inner salts having equal number of positively- and negatively-charged portions in their molecules. The common types of detergents, many of which are being widely used for cleaning and disinfecting the clothes, utensils and all types of washable equipment of the COVID-19 patients and the medical professionals, have a number of adverse

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effects on human health as well as on the ecosystem (Fig. 6.5). For a detailed discussion on this subject, the review of Mousavi and Khodadoost (2019) may be referred. A few salient points on the health and environmental impacts of detergents are listed below (after Effendi et al. 2017; Gfatter et al. 1997; Hill 2021; Nielsen et al. 2000). (i)

When applied for washing clothes and cleaning other objects, the detergents come into contact with human skin, and may cause contact dermatitis (a type of skin rash) to sensitive groups of individuals. It may also promote percutaneous absorption (i.e., absorption through the skin) of toxic chemicals. In comparison to alkaline soaps, however, the detergents cause much less increase of skin pH (Gfatter et al. 1997). (ii) Some of the widely used detergents evidently increases the skin permeability, thus causing penetration of foreign substances. Nielsen et al. (2000) have experimentally shown that the effects of the non-ionic detergents on skin permeability was not less than those of the anionic and cationic detergents. (iii) The surfactants in the detergent, if ingested, can damage the endocrine systems of humans and animals. (iv) Bleaching agents added to the detergents, like sodium perborate, may cause irritations in the nose, eyes, lungs and skin, and may also affect reproductive health. (v) Phosphate-containing detergents can trigger excessive growth of some types of algae in freshwater bodies, which consumes all the oxygen available in the water. This process, known as eutrophication, may lead to continual oxygen depletion, and may also bring about release of toxins. Decomposition of the algae in water leads to further depletion of oxygen (Effendi et al. 2017, Cohen and Keiser 2017). All these result in the death of a large number of natural aquatic plants and animals, and serious damage to the freshwater ecosystem. (vi) Many fishes and some other aquatic animals have a protective mucus layer on their surfaces that protect them from microbial infections. Surfactants in detergents damage that protective covering, making them vulnerable to viruses, bacteria and all types of parasites. (vii) By lowering the surface tension of the water, the surfactants also promote the easy absorption of different anthropogenic toxins like pesticides, phenols etc. by the fish. A detergent concentration of only 2 ppm can cause two-fold absorption of chemicals by the fish, which may lead to their death. (viii) Chemicals like nonylphenol ethoxylates that are commonly used in the detergents, and different types of dyes, are harmful to aquatic life. Some of them are even reported to be carcinogens. (ix) The studies of Effendi et al. (2017) indicate that detergents significantly decrease the growth of bacterial population in the sea water. Higher level of detergents in the water, and longer periods of their exposure, cause greater impacts on the marine bacterial populations.

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6.3 Clays in Covid-19 Prevention: Disinfectants that Are Safe for Human Health and Environment Very fine flakes of clay minerals, owing to their negatively charged surfaces and high specific surface areas, have a higher affinity to bacteria and viruses than most other minerals (see Chap. 1, Sects. 1.4 and 1.6 for detailed discussion). Nano-clays are naturally occurring or artificially produced nano-sized flakes of clays. In many instances, the bond between the virus spike protein and the nano-clay particles was found to be much stronger than that between the viruses and the hACE2. The binding capacity of a material can be quantitatively expressed as its Cohesive Energy Density (CED), which is the measure of the mutual affinity/attractiveness of molecules arising from the electrostatic forces and also the Van der Waals forces. Abduljauwad et al. (2020) carried out molecular-level simulations and modelling to study the interaction of coronavirus spike with hACE2, in the presence and absence of nano-clays. They reported that the CED of SARS-CoV-2 is only ~1 J/cm3 with hACE2, but starts from ~10 J/cm3 with nano-clay crystallites, and can be as high as 154 J/cm3 with increasing concentration of clay molecules (see Fig. 4 and Fig. 5 of Abduljauwad et al. 2020). The attachment of the SARS-CoV-2 spike with nano-clay particles is therefore much stronger than that with the hACE2. This attribute of the clay minerals facilitates their application as potential disinfectants against the SARS-CoV-2 virus, which can be successfully utilised for the prevention of COVID-19 (Fig. 6.6).

6.3.1 Clay-based Hand Sanitisers Hand sanitizers may be produced from bentonites and some other types of clays, which are free from all the hazardous aspects of alkali-based soaps and ABHS listed in Sect. 6.2. Furthermore, they are beneficial to the skin in many respects, like healing a number of skin infections, and removing the dead skin cells to improve its look. Das and Tadikonda (2020) proposed the use of bentonite paste to prevent the hand to hand transmission of SARS-CoV-2 and other pathogens which are transmitted in similar ways. The thin flakes bentonite clays, being predominantly composed of montmorillonite, are characterized by a very high specific surface area and cation exchange capacity (see Chap. 1, Sects. 1.4 and 1.6). The strong attachment of the SARS-CoV-2 protein spikes with the charged montmorillonite surface, due to the very high CED between them, ensures a complete (100%) adsorption of the virus in presence of sufficient quantity of bentonite. This prompted Das and Tadikonda (2020) to propose a technique of using a bentonite clay paste for hand sanitisation. While applied on the hand, that paste is expected to adsorb all the virus from the skin, after which washing with fresh water will remove the clay particles along with the adsorbed viruses (Fig. 6.7).

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Fig. 6.6 Prospective applications of clays for the prevention of COVID-19 infection. See Sect. 6.3 for detailed discussion. [Graphic works by the authors]

More effective clay-based disinfectants may be produced by the combination of clay minerals with other inorganic and/or organic substances. Some of the inorganic antimicrobial clay derivatives, however, contain heavy metals, which may have detrimental effects on prolonged applications (Hoang et al. 2021). Organoclay materials can be considered as safer alternatives, which are hybrid materials resulting from the association of clay minerals with organic surfactants and/or other types of organic compounds. These materials are generally synthesised from the clay minerals with high swelling capacities, such as montmorillonite, vermiculite, saponite etc., by substituting their original interlayer cations with organic cations. The internal

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Fig. 6.7 Risk-free, healthy technique for hand sanitisation with bentonite paste, as suggested by Das and Tadikonda (2020). [Graphic works by the authors]

lamellar structures of the original clay minerals are preserved in them. The organoclays have organophilic surfaces, consisting of covalently bonded organic moieties [A ‘moiety’ is a specific group of atoms within a molecule that is responsible for characteristic chemical reactions of that molecule. A similar term is ‘functional group’, which is generally applied to a smaller group of atoms] (Guégan 2019; Helmenstine 2020). Aminoclays are tailor-made organoclay material, having the chemical name 3-Aminopropyl functionalized magnesium phyllosilicates (Yang et al. 2014). They have many biomedical applications, and are widely used as organoclay based drug carriers. Hoang et al. (2021) formulated a clay based antimicrobial hand gel by combining the zinc-aminoclay (ZnAC) and the extract of a cactus species called Opuntia humifusa (Family Cactaceae). ZnAC was produced by dissolving ZnCl2 .2H2 O in ethanol solution, followed by a drop-wise addition

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of 3-aminopropyltrielthoxysilane. The ZnAC thus obtained in slurry form was centrifuged, washed with ethanol, and dried in oven to produce ZnAC powder with zeta potential of +40.90 mV. The extract of O. humifusa was prepared by washing and grinding its raw leaves in a blender, and subjecting it to microwaves in a domestic microwave oven for sufficient time. A pure extract solution was obtained by removing the insoluble impurities through centrifugation and filtering. Finally, the hand gel was produced by mixing the ZnAC and the O. humifusa extract with glucomannan and glycerol in a specific ratio. While the antimicrobial properties of ZnAC in this hand gel disinfect the hands of the users, the O. humifusa extract is expected to protect their hand skin from dryness caused by frequent hand washing. The authors claimed this formulation to be more preferable than the conventional hand sanitisers for the following reasons: (i)

Effective antimicrobial activity, which was claimed to be similar to that of ABHS. (ii) Negligible toxicity. (iii) Moisturizing effect that saves the skin from desiccation and damage. (iv) Very low clinical irritation.

6.3.2 Clay-based Surface Disinfectants Das and Tadikonda (2020) recommended a method for disinfecting the contaminated medical gears with clays, which involves spraying the bentonite slurry on the contaminated surface, and then washing with water. Such a process of surface sanitisation, if used effectively, is capable of preventing the transmission of SARS-CoV-2 by dermal contact. Furthermore, substitution of the widely used conventional surface disinfectants with the clay-based sanitisers is expected to protect the human health as well as the environment from the extremely detrimental effects of alcohols and detergents, listed in Sects. 6.2.2 and 6.2.3 respectively. Among the different types of clay minerals, those belonging to the smectite group (especially montmorillonite) and vermiculite group are found to be most effective as surface disinfectants. Da Silva-Valenzuela et al. (2014a, b) characterised four types of clays for detergent formulation: one purified bentonite, two natural bentonites, and one natural kaolin. They reported that the purified bentonite was the most appropriate material for use in clay production, by virtue of its suitable rheology, pH, swelling capacity, CEC, and absence of sediment impurities. However, the use of these clays for washing medical gears have one disadvantage: the transition elements (mainly iron) in their octahedral cationic sites may discolour the clothes. White clay minerals, such as kaolinite, can be considered for the production of clay-based detergents, and further research are highly recommended on this subject.

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6.3.3 Clay Preventing Airborne Virus Propagation Mishra et al. (2020) suggested a method of treatment of the COVID-19 patients that may effectively utilise the disinfectant properties of clays for preventing further propagation of this disease. A sanatorium-like establishment, with all medical facilities, is to be constructed in about half-an-acre of protected land in rural areas. There should be sufficient open spaces and bare soil surrounding the buildings. The soil in this protected land is to be treated with NaOCl, to destroy the pathogens on the ground surface and in the aerosol above the ground. Then an appropriate number of COVID-19 patients may be transferred there, and their treatment should be continued, maintaining physical distancing and other requirements as prescribed by the WHO. The presence of clay minerals in the exposed soil surface and in the windblown fine dust particles in aerosol is expected to decelerate further multiplication of SARSCoV-2, as well as its transmission from one person to another. This inexpensive but potentially efficacious methodology may be applied in the initial stage of a wave, when the number of infected persons is small, to save the larger population from the infection.

6.3.4 Clay Against Virus Propagation from Biomedical Wastes Biomedical wastes (also called hospital/biohazardous/infectious wastes) are the different types of waste materials containing infectious or potentially infectious substances. These include the blood and body fluids of diseased humans and animals, laboratory wastes containing infectious pathogens (e.g., discarded specimen cultures, live or attenuated viruses), pathological wastes, etc. Considering the extremely high infectivity of SARS-CoV-2, the biomedical wastes generated from the COVID-19 treatment centres, pathological laboratories or the houses of patients are very likely to be the sources of widespread infections. If not properly taken care of, the disposable or non-disposable medical gears and different equipment associated with the treatment of COVID-19 patients may also be the sources of SARS-CoV-2 propagation. Burning these biomedical wastes is a commonly used measure to destroy the virus contained by them. But although it can prevent infections, open air burning of plastic bags, pipettes, and many other materials in the wastes may release a large number of hazardous toxins in nature. Das and Tadikonda (2020) studied the possibility of disposing off such wastes in a barrier system of 2–3 mm thickness, constructed exclusively of montmorillonite and kaolinite; and claimed that this environment-friendly way of waste disposal can contain the SARS-CoV-2 and some other pathogens for fifty years.

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6.4 Prospective Application of Clays in the Treatment of COVID-19 Any significant development regarding the successful application of clay-based drugs in the treatment of COVID-19 is yet to be reported. However, there are ample evidence to suggest that the antimicrobial actions and other characteristic properties of the clay minerals may be utilised in this field, as specified below. (a) Various accounts of early medical treatments testify to the oral application of clays in the treatment of gastro-intestinal diseases caused by viruses similar to SARS-CoV-2 (Abehsera 1979). Also, a number of scientific investigations carried out within the last 20–30 years testify to the successful application of clays in the treatment of coronavirus-induced diseases of other animals (Clark et al. 1998). (b) Some recent studies suggest that new drugs may be developed from nano-clays and different types of clay derivatives that can prevent the attachment of the virus to human cells (Abduljauwad et al. 2020; Poeta et al. 2021). (c) Several researchers have established that the repurposing of earlier drugs may be successfully used in the treatment of COVID-19, and the efficacy of these drugs increases significantly when a clay-based drug delivery system is used (Piao et al. 2021; Teodorescu and Morariu 2022). In the light of all these investigations, this section presents a brief discussion on the prospects of the application of clays against SARS-CoV-2 and similar pathogens.

6.4.1 Clays in the Treatment of Similar Viruses The bovine coronavirus or BCoV, along with rotaviruses, are the leading causes of acute gastroenteritis of the calves and the young of other mammalian and avian species. Like the SARS-CoV-2, the BCoV belong to the family Coronaviridae in the order Nidovirales, and these two viruses have many similarities in their structural and functional characteristics: both are pleomorphic, enveloped RNA viruses, having diameters within the range of 65–210 nm, and have their envelopes covered with glycoprotein spikes (Saif 2010). Like other enveloped viruses, BCoV is sensitive to detergents and lipid solvents (e.g., ether, chloroform) and can be inactivated by conventional disinfectants, formalin, and heat. Clark et al. (1998) tried to find out some alternative broad spectrum methods for the treatment of acute diarrheal diseases of cattle caused by the bovine coronavirus and rotavirus. Their studies revealed that some clays, a group of clay derivatives named HSCAS (hydrated sodium calcium aluminosilicate clay), and a few non-clay adsorbents have excellent capabilities of adsorbing bovine coronaviruses, with >90% adsorption. They inferred that the virions were attached to the outer surface of each adsorbent particle. They further postulated that the prophylactic use

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of adsorbent agents (feeding adsorbent agents daily) could decrease enteric viral infections by binding with the viruses in the intestines. But this hypothesis was not empirically confirmed. Nevertheless, considering the structural and functional similarities of BCoV with SARS-CoV-2, such investigations point to the high probability of the development of new clay-based medicines for COVID-19, especially for the treatment of the infected gastrointestinal tract. Some researchers have already recommended clay minerals for this purpose, as described in the next subsection.

6.4.2 Prospects of Developing Drugs from Nano-Clays for Healing SARS-CoV-2 Some COVID-19 patients suffer from diarrhoea when the SARS-CoV-2 enters their intestine, and are attached by the spike protein to the hACE2 receptors in the enterocyte apical membranes. The physicians earlier treated COVID-19-induced diarrhoea by the medications that could relieve the symptoms and stop the further spreading of the virus within the gastrointestinal tract. Poeta et al. (2021) tested the trapping and anti-inflammatory properties of di-octahedral smectite or diosmectite in a SARS-CoV-2 model. They reported that diosmectite could bind the spike protein receptor-binding domains and SARS-CoV-2 preparation, and inhibited the attachment of spike protein with the hACE2 receptors. Diarrhoea brings about damages in the inner mucus lining of the large intestine, causing swelling and inflammation. Citing direct evidence of the trapping of SARS-CoV-2 components by clays that stopped the diarrhoea-induced inflammation, Poeta et al. (2021) recommended the application of diosmectite for the treatment of diarrhoea associated with COVID-19. Abduljauwad et al. (2020), on establishing empirically the greater affinities of nano-clays to the SARS-CoV-2 spikes than the hACE2 (explained in Sect. 6.3), discussed the applicability of nano-clays in the treatment of COVID-19. They postulated the development of “clays-alone” medicines to resist the SARS-CoV-2, recommending future in vitro and in vivo investigations on this subject. The ultra-fine clay flakes released from such medicine are expected to bind strongly to the spike protein of the virus and remove them from the diseased body (Fig. 6.8a and b). An antibody is a type of protein produced by the immune system of an animal in response to the antigens (pathogens and toxic materials), which engulf those antigens and remove them from the body. Since the proposed nano-clay-based medications are expected to latch upon the viruses and remove them from the system, thus mimicking the actions of antibodies, Abduljauwad et al. (2020) called them “pseudo-antibodies” against SARS-CoV-2. This term has been accepted and used by other researchers also. In spite of all the anticipated or proven potentialities of clays or their derivatives to resist the SARS-CoV-2 virus, their direct administration to the COVID-19 infected patients is yet to be started. Production of effective clay-based drugs or injections for

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Fig. 6.8 Prospective applications of clays for healing COVID-19 patients. a Nano-clay based “clays-alone” drug proposed by Abduljauwad et al. (2020). b Nano-clay particles attach to spike protein of SARS-CoV-2, and remove the virus from the system. See Sect. 6.4.2 for detailed discussion. c Repurposed anti-COVID-19 drug, e.g., NIC or Rif, encapsulated in clay-based drug delivery system. See Sect. 6.4.3 for explanation. d Expected dual actions of clay-encapsulated anti-COVID-19 drug. See Sect. 6.4.4 for explanation. [Graphic works by the authors]

the treatment undoubtedly requires further scientific and technological research. The molecular-level simulation and modeling studies carried out so far may be considered as a veritable first step towards achieving that goal.

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6.4.3 Clay in the Drug Delivery Systems of Anti-COVID-19 Medications A drug delivery system (DDS) is a formulation or a device that enables a drug to selectively reach its site of action, without affecting the other cells, organs, or tissues that are not the targets of that drug. The formulations used in the DDS generally do not have healing properties of their own, but they can improve the efficacy of drugs, and facilitate the safe introduction of drugs in the body by controlling the rate, time and place of their release. Clay minerals, especially montmorillonite, kaolinite, and halloysite, have the abilities of effective drug incorporation, delayed or controlled drug release, and enhancement drug dissolution, all owing to their following characteristic properties (after Khatoon et al. 2020). (i) (ii) (iii) (iv) (v)

Good biocompatibility with various types of drugs High surface charge High specific surface area Chemical inertness Non-toxicity

There have been extensive studies on the vast applications of clay minerals in DDS. We restrict this discussion to the advantages of using clays and their derivatives in the delivery systems of anti-COVID-19 medications. (a) Repurposing of Drugs Since the outbreak of the present pandemic, scientists have been looking for all the feasible options in search of the appropriate medicines for COVID-19. The promising options found so far include the applications of diverse types of nanomaterials and the repurposing of old drugs. While the classical approach of the discovery of new drugs may take a lot of time and effort, repurposing of suitable old drugs to develop new, effective medications provides a less time-consuming, economical solution, which is of much help during medical emergencies like the present pandemic situation. Drug repurposing or repositioning is the application of an old drug, which was approved by an appropriate authority (like the Food and Drug Administration of USA), outside its original treatments. This involves the identification of possible new disease targets for that old drug. Many researchers throughout the world are investigating the applicability of the previously certified drugs that were effective in the treatment of similar viral diseases such as MERS, SARS, etc. in their quest for proper anti-COVID-19 treatments (Gowri and Anand 2021; Pishva and Yüce 2021; Saul and Einav 2020; Sivasankarapillai et al. 2020; Srivastava et al. 2021; Teodorescu and Morariu 2022). (b) Repurposed Niclosamide in Clay-based DDS in the Treatment of COVID-19 Niclosamide (NIC) is an orally administered anthelmintic (i.e., anti-parasitic) drug widely used for the treatment of parasitic diseases. Recent studies have revealed that repurposing of this drug may facilitate the treatment of diseases other than

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those caused by parasites, including COVID-19, since it could be successfully used in the treatment of many viral diseases like MERS, SARS, Japanese encephalitis, chikungunya, etc. It has also been proved to be effective against some other viruses like Zika virus, human adenovirus, Epstein–Barr virus, etc. Since the new SARSCoV-2 virus has some similarities with these pathogens, it is widely believed that an appropriately modified version of NIC can be effectively used in the treatment of COVID-19 as well (Gassen et al. 2019; Huang et al. 2017; Marrugal-Lorenzo et al. 2019; Piao et al. 2021; Sun et al. 2013; Wang et al. 2016; Wu et al. 2004; Xu et al. 2016). However, the low solubility of NIC in aqueous solution results in its poor bioavailability, which significantly reduces the efficiency of this drug. To solve this problem, Piao et al. (2021) formulated an orally-administered drug comprising NIC molecules encapsulated in different types of mesoporous silica biomaterials. Mesoporous substances are characterised by nano-sized porosities (pore diameters in between 2 and 50 nm; Rouquerol et al. 1994) with ordered hexagonal structures, sufficient pore volumes, and large surface areas. Among the materials used by Piao et al. (2021), a mesoporous geopolymer produced from kaolinite was reported to be very effective drug carrier with high NIC loading capability and increased NIC solubility. It was developed by dissolving kaolinite in an aqueous alkali solution. The alkaline activation and de-hydroxylation treatments associated with its synthesis resulted in the partial substitution of tetrahedral Si4+ of the kaolinite by Al3+ and consequent incorporation of the alkali ions like Na+ for balancing the excess negative charge. The presence of Na+ in the pore spaces of this geopolymer enabled the encapsulation of NIC drug molecules by ion–dipole interaction and a controlled release of these molecules through modification of the CEC. The release of NIC was reported to increase in the presence of simulated gastric fluids and intestinal fluids. (c) Repurposed Rifampicin in Clay-based DDS in the Treatment of COVID-19 Repurposing of the anti-tubercular drug Rifampicin (Rif) also shows promising results in the treatment of COVID-19. Introduced in the treatment of tuberculosis nearly 50 years ago, Rif (C43 H58 N4 O12 ) was found to be one of the most efficient anti-tubercular drugs yet discovered. Many antiviral drugs destroy the virus by targeting their proteases, which are the enzymes encoded by the viral DNA or RNA to perform proteolytic events (hydrolysis of proteins or peptides) that are essential for the completion of the infectious cycle (Steinkühler 2008). In silico investigations or molecular docking studies (computational simulation processes of studying how two or more molecules fit together) indicated that the Rif can target the main protease of SARS-CoV-2, and has a very strong binding affinity with it. The repurposed drug formulations of Rif with suitable drug delivery systems can therefore be considered as potent inhibitors of COVID-19 (Gupta and Zhou 2020; Mamidala et al. 2021; Pathak et al. 2020; Soni et al. 2020). Teodorescu and Morariu (2022) recommended an anti-COVID-19 formulation loaded with Rif, comprising a drug delivery system made of laponite and polyvinyl alcohol. Laponite [Na(LiMg8 )Si12 O30 (OH)6 ] is a synthetic derivative of the clay mineral hectorite, trioctahedral smectite having the composition Na0.3 (Li,

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Mg)3 Si4 O10 (OH)2 and the characteristic t–o–t–c internal structure (Anthony et al. 1995; Bergaya et al. 2006; Chap. 1). The drug delivery system was a hydrogel synthesized by entrapping laponite in a matrix of polyvinyl alcohol using the freezing/thawing method. In vitro studies and in silico molecular docking simulations performed by Teodorescu and Morariu (2022) proved that the morphological, rheological, and swelling properties of this clay-based hydrogel are appropriate for the drug delivery system of Rif and other repurposed anti-COVID-19 drugs.

6.4.4 The Expected Synergistic Actions of Clay-based Drugs: Double-Edged Swords Against COVID-19? Medication can effectively resist a virus if it has any one of the following potentialities: (i)

To target the functional proteins and enzymes (like viral proteases) that are vital for the survival and infectivity of the virus. (ii) To inhibit the attachment of the human protein receptors (like hACE2) with the virus. (iii) To block the interaction of viral structural proteins with the host cells. (iv) To stimulate the human immunity. The clay-based formulations, as the preceding discussions indicate, possess one of the above four potentialities [no. (ii)], and can be used in the delivery system of drugs that possess another [no. (i)]. (a) Clay derivatives can be used in the delivery system of anti-COVID-19 drugs (e.g., NIC, Rif, etc.) and enhance their efficacy, as reported by Piao et al. (2021), Teodorescu and Morariu (2022). See Sect. 6.4.3 for further details. (b) Nano-clays can interact with the virus spike proteins and inhibit their adhesion to the hACE2 receptors, as indicated in the studies of Abduljauwad et al. (2020) and Poeta et al. (2021). See Sect. 6.4.2 for further details. It can, therefore, be postulated that it is possible to develop drug delivery systems with the appropriate clay-based nano-hybrids that have dual actions against the SARS-CoV-2 (Fig. 6.8c and d). This anticipated synergistic effect gives the clay nanocomposites an edge over the other drug carriers for the anti-COVID-19 drugs. Concluding Remarks The rapid spread of COVID-19 over huge populations has forced people into the excessive use of disinfectants that are either alkaline (like soaps and detergents) or alcohol-based. The potentially harmful effects of these conventional disinfectants, however, call for the exploration of other safer alternatives. Furthermore, the limitations of the conventional therapeutic systems to address the situation compels the researchers to look for new types of medicines. This chapter explains why claybased disinfectants are preferable over the commonly used ones in many situations.

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The prospects for production of risk-free, environment-friendly disinfectants for the prevention of the spreading of COVID-19 have been discussed in detail. Also, some state-of-the-art investigations have postulated that some qualities of the clay minerals can be utilised to cure this disease. There are enough laboratory evidence to suggest that nano-clay-based drugs can be developed that will be attached to the SARS-CoV-2 and removed from the bodies of infected persons. Repurposed medicines encapsulated in clay-based drug delivery systems, in addition, are expected to destroy the virus with synergistic effects. The materialisations of such schemes discussed in this chapter, however, require intensive research on this subject, and an integrated effort of trans-disciplinary workers including mineralogists, material scientists, biochemists, virologists, and medical professionals.

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Teodorescu, M. and S. Morariu (2022). Drug delivery system based on PVA and clay for potential treatment of COVID-19. Journal of Polymer Research, 29(2): 67. https://doi.org/10.1007/s10 965-022-02927-5. Thanh, Tn. (2020). Homemade disinfectant spray recipes. https://relief.unboundmedicine.com/ relief/view/CoRespond-Emerging-Topics/2425043/all/Homemade_disinfectant_spray_recipes. Last visited: 22/11/2021. Tomás, H., Alves, CS. and J. Rodrigues (2018). Laponite®: A key nanoplatform for biomedical applications? Nanomedicine Nanotechnol. Biol. Med., 14: 2407–2420. https://doi.org/10.1016/j. nano.2017.04.016. Tonini, S., Dellabianca, A., Costa, C.M., Lanfranco, A., Scafa, F. and S.M. Candura (2009). Irritant vocal cord dysfunction and occupational bronchial asthma: differential diagnosis in a health care worker. Int. J. Occup. Med. Environ. Health, 22: 401–406. Turner, A.J. (2015). Chapter 25: ACE2 Cell Biology, Regulation, and Physiological Functions. In: Unger, T., Ulrike, M., Steckelings, U.M., dos Santos, R.A. (eds). The Protective Arm of the Renin Angiotensin System (RAS): Functional Aspects and Therapeutic Implications. Academic Press. pp. 185–189. https://doi.org/10.1016/B978-0-12-801364-9.00025-0. Voss, A. and A.F. Widmer (1997). No time for handwashing!? Handwashing versus alcoholic rub: Can we afford 100% compliance? Infect. Control Hosp. Epidemiol., 3: 205–208. WHO (2022). Tracking SARS-CoV-2 variants, https://www.who.int/en/activities/tracking-SARSCoV-2-variants/. Wang, B., Zhang, A., Sun, JL., Liu, H., Hu, J. and Xu, LX. 2005. Study of SARS transmission via liquid droplets in air. J. Biomech. Eng., 127: 32–38. Wang, J., Jiang, M., Chen, X. and L.J. Montaner (2020). Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J. Leukoc. Biol., 108(1): 17–41. Wang, Q. (2020). hACE2 transgenic mouse model for coronavirus (COVID-19) research. Research Highlight February 24, 2020. https://www.jax.org/news-and-insights/2020/february/introducingmouse-model-for-corona-virus. Wang, Y.-M., Lu, J.-W., Lin, C.-C., Chin, Y.-F., Wu, T.-Y., Lin, L.-I., Lai, Z.-Z., Kuo, S.-C. and H.-J. Ho (2016). Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission. Antivir. Res., 135: 81–90. Watanabe, Y., Allen, J.D., Wrapp, D., Mc Lellan, JS. and M. Crispin (2020). Site-specific glycan analysis of the SARS-CoV-2 spike. Science, 369: 330–333. Wrapp, D., Wang, N., Corbett, K., Goldsmith, J., Hsieh, C. and O. Abiona (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367: 1260–1263. Wu, C.-J., Jan, J.-T., Chen, C.-M., Hsieh, H.-P., Hwang, D.-R., Liu, H.-W., Liu, C.-Y., Huang, H.- W., Chen, S.-C. and C.-F. Hong (2004). Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob. Agents Chemother., 48: 2693–2696. Xu, M., Lee, E. M., Wen, Z., Cheng, Y., Huang, W.-K., Qian, X., Julia, T., Kouznetsova, J., Ogden, S.C. and C. Hammack (2016). Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat. Med., 22: 1101–1107. Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H. and X. Li (2020). Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China Life Sciences, 63(3): 457–460. https://doi.org/10.1007/s11427-0201637-5. Yang, L., Lee, Y., Kim, M., Park, H.G., Huh, Y.S. Shao, Y. and H.K. Han (2014). Biodistribution and clearance of aminoclay nanoparticles: Implication for in vivo applicability as a tailor-made drug delivery carrier. Journal of Materials Chemistry, B2(43): 7567–7574. Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J. and H. Liu (2020). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med., 8: 475–481.

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Yu, S., Piao, H., Rejinold, N.S., Jin, G., Choi, G. and J.-H. Choy (2021). Niclosamide–clay intercalate coated with nonionic polymer for enhanced bioavailability toward COVID-19 treatment. Polymers, 13: 1044. Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L. and Zhang, W. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798): 270–273. https:// doi.org/10.1038/s41586-020-2012-7. Ziemba, R., Campbell, K.N., Yang, T.H., Schaeffer, S.E., Mayo, K.M., McGann, P., Quinn, S., Roach, J. and E.D. Huff (2021). Excess death estimates in patients with end-stage renal disease – United States, February-August 2020. MMWR Morb Mortal Wkly Rep., 70(22): 825–829. Zou, X., Chen, K., Zou, J., Han, P., Hao, J. and Z. Han (2020). The single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection. Front. Med., 14: 185–192.

Chapter 7

The Present and the Future: Advantages, Drawbacks, and Future Prospects of Clays for Protection of Human Health

Introduction The antimicrobial and antitoxic properties of clay minerals, as described in this book, have been utilised by mankind since the earliest days of human civilisation. However, the production of therapeutic agents have evolved immensely after the industrial revolutions and the rapid advancements in sciences and technologies in the last couple of centuries. The applications of clay minerals in the various fields of pharmaceutical industries have also increased manifold in recent years. From the elaborate discussions given in Chaps. 4, 5 and 6, it may certainly be predicted that there are ample scopes for better utilisation and broader applications of the antimicrobial and antitoxic properties of clay minerals in the formulation of new, more powerful substances for the protection of the human health. It is to be taken into account that the same antimicrobial and antitoxic properties of the clay minerals can also be utilised in diverse fields of waste management and environmental protection. Removal of organic and inorganic pollutants, herbicides and pesticides, excess chemical fertilisers, etc. from the soil or water bodies are some of the important environmental applications of natural clays, clay minerals, or their derivative products. But conforming to the objective of this book, we restrict this discussion to the therapeutic applications of the clay minerals only. The interested readers may consult Sects. 11.1 to 11.4 of Bergaya et al. (2006), and Chaps. 20 and 21 of Mukherjee (2013) for some general ideas on the applications of clays in environmental protection and waste management. Ghosh and Mukherjee (2019) may also be referred for a comprehensive review of the recent research on the protection of the soil environment from the detrimental impacts of modern agricultural practices. This chapter explains the major advantages of using the clay minerals over the other therapeutic agents, disinfectants, etc. (Sect. 7.1), and the application of nanotechnology for synthesizing more effective antimicrobial agents from these minerals (Sect. 7.2). Some possible drawbacks associated with large-scale production of clay-based medicines and nanomaterials have been described in Sect. 7.3.

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Finally, the chapter concludes with Sect. 7.4 which recommends some areas of future research, which are expected to help in producing more effective antimicrobial and antitoxic agents from the clay minerals, and finding new therapeutic applications for them.

7.1 Advantages of Clay Minerals Over the Other Medicine Ingredients Since the early days of human civilisation, medicine men, physicians, chemists, pathologists, and scientists of different disciplines are searching for a panacea, which is supposed to cure all types of ailments. But what they have given us instead is the opposite of that—more than one type of medicine for each disease! Even when the diseases are correctly diagnosed, there may be a significant contradiction regarding the selection of the correct medicine. Each medicine, or to be more specific, each constituent in a particular type of medicine, has some certain advantages and disadvantages of its own; based on its effectuality for the desired function, side effects, economic considerations and environmental impacts. The clay minerals, whether used as the active ingredient in medicine or as an excipient (see Sect. 4.2, Chap. 4), have certain advantages over many other mineral and non-mineral constituents of medicines, as described in this section. The major advantages of the applications of clay minerals and their products in the medical industry have been reviewed by many authors (e.g., Adekeye et al. 2020; Carretero 2002; Carretero et al. 2006; Gomes and Silva 2007). Some of the most important points are described here.

7.1.1 Therapeutic Considerations (a) Applications of antimicrobial actions: As described elaborately in Chap. 4, the antimicrobial actions of the clay minerals and their synthetic composites can be fruitfully utilised in the treatment of a large number of common diseases. The physical and chemical properties of the clay minerals, which enable them to remove viruses and assist in the bactericidal reactions, have been explained in Sects. 2.1 and 2.2 of Chap. 2. Such properties are not commonly observed in other natural inorganic and organic substances. (b) Applications of antitoxic attributes: The detailed discussion given in Chap. 5 indicates that the antitoxic properties of the clay minerals can be successfully exploited to protect human health from many common types of external or internal toxins. The unique properties of the clay minerals to adsorb the toxin molecules in their interlayer spaces, and the associated physical and chemical processes, have been described in Sect. 2.4 of Chap. 2.

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(c) Ability to combine with other substances: The clay minerals can easily bind to a wide variety of antimicrobial metals and organic molecules in their interlayer spaces. The composite materials thus produced can be used to prepare more powerful therapeutic agents and more effective tailor-made medicines for certain diseases. See Sect. 2.3 of Chap. 2 and Sect. 6.3.1 of Chap. 6 for a detailed discussion on this subject. Nanotechnology has enabled the production of another category of composite and hybrid materials, by combining nanoparticles of clay minerals and other substances (generally polymers and different drugs). Such materials have some unique properties that make them suitable for the production of more effective therapeutic agents. See Sect. 7.2 of this chapter for an elaborate discussion on this subject.

7.1.2 Economic Consideration (a) Abundance and easy availability: Clay minerals are more abundant in nature than the other commonly used constituents of medicines, and they are readily available in almost every inhabitable place of the world. (b) Easy purification: Traditionally, in indigenous therapeutic systems, the natural clays are generally cleansed of some associated minerals and associated phases before their topical or oral applications. The clay-based medicine industries require further refinement of the natural clays and sometimes separation of some desired clay minerals from them. These purification processes are not very difficult or expensive. (c) The production of more effective, tailor-made medicines from the claynanocomposites [see point number Sect. 7.1.1(c) above], by combining the suitable clay minerals with other materials, are usually a simple, low-cost process. Less expensive but more effective medicines can therefore be produced from the clays. For all the three reasons mentioned above, the natural clays are preferable to most of its common substitutes from the economists’ point of view.

7.1.3 Health and Environmental Considerations (a) Risk-free for human health: A major advantage of the clay minerals is that the medicines in which they are used as the active ingredients are not usually harmful to human health. The clay-based drugs generally have much fewer side effects than many other medicine constituents. (b) Environment-friendly medicines: In many situations, the medicine plants are the major sources of water and soil pollution. A huge quantity of therapeutic

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agents used in the treatment of humans and domestic animals, including the medicines for cancer treatment, antibiotics, etc., and many chemicals used in agriculture and aquaculture, like antifungals and parasite-killers, can severely contaminate the surface waters bodies and soil over certain areas. It takes a lot of time for the natural processes to remove these substances (or their altered products) from the contaminated water or soil, and alleviate their detrimental effects. They are released in nature in the following ways (after Boxall 2004; Owens 2015). (i)

(ii) (iii)

(iv)

(v)

(vi)

The residues of these medicines and their associated products (which may also be harmful) may be released through the sewer systems of the medicine production plants. Some amount may also be leached out from the solid waste disposal sites of those plants. The sewage and leachate may then find their way to the surface water bodies and contaminate them. Soil may be directly contaminated by the disposal of solid wastes, and also from the contaminated water bodies. After consumption, these medicines or their metabolic products are excreted from human bodies and are released to nature through the sewer networks of hospitals or domestic areas. Fungicides and parasite killers used in agriculture and horticulture are directly released into the soil, a part of which may also be transported into the surrounding surface water bodies by rainwater. Antibacterial substances for the treatment of fish or shrimp are directly mixed with the waters of the rearing tanks, from which they may also contaminate the other connected surface water bodies. The disposal sites of unused and expired medicines are also potential sources of contamination.

The clay-based therapeutic agents, in contrast, are much less harmful to the environment than the above medicines. Unlike the effluences of other medicine factories, the waste products released from clay-based medicine plants are less hazardous to the health of the industrial workers and the people residing in surrounding areas. The medicines in which clays are used as the chief ingredients generally do not have any major detrimental effects on soil and water. The medicines where the clays are used as excipients with potentially toxic active ingredients when released in water, may contaminate it like the other medicines. But the associated clay minerals may probably adsorb some amount of toxins from the water and reduce the contamination, at least to some extent. The abilities of the clay minerals to adsorb such toxins have been discussed in Sect. 5.2 of Chap. 5, and the associated mechanisms are explained in Sect. 2.4 of Chap. 2.

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7.1.4 Better Alternative for Preventing the Spread of Infectious Diseases The abilities of the clay minerals to disinfect human skin and other surfaces make them suitable for the production of sanitizers and disinfectants. The conventional sterilising agents, like the alkali-based soaps, detergents and alcohol-based disinfectants, have a large number of detrimental effects on human health and the environment, as explained in Sect. 6.2 of Chap. 6. The clay-based disinfectants, on the other hand, are environment-friendly and do not harm human skin, as explained in Sect. 7.1.3(vii) and (viii) above; although they are equally (if not more) effective than the conventionally used disinfectants. See Sect. 6.3 of Chap. 6 for a comprehensive discussion on a number of theoretically postulated as well as empirically proven applications of clay minerals in the prevention of the spread of the SARS-CoV-2 virus. The claybased formulations for surface and hand sterilisers recommended there can prevent the propagation of other viruses and bacteria also.

7.2 Antimicrobial Applications of Clay Nanocomposites and Clay-Drug Nanohybrids Nanoparticles are particles with one or more dimensions at the nanoscale, i.e., in the order of 100 nm or less [1 nm (nm) = 10–9 m or millionth of a millimeter]. The properties of nanoparticles differ significantly from the larger scale particles of the same material. The nanomaterials show many unique characteristics that are not found in the same material without nanoscale features. Nanotechnology, which is one of the most promising and rapidly evolving disciplines of modern technology, involves the manipulation of atoms and molecules at nanoscale, for designing, producing, and using structures, devices, and systems (after SCENIHR 2006). Nanotechnology is one of the youngest, rapidly emerging fields of modern technology, which has heralded revolutionary advancements in many other fields of science and technologies, including the medical sciences. To provide some basic ideas on this subject, this section gives an overview of the manifold applications of nanotechnology in various fields of medical sciences and the properties and production of clay nanocomposites. This discussion has been concluded by highlighting some areas for future research on clay-based nanocomposite and nanohybrid medicines.

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7.2.1 The Multifaceted Applications of Nanotechnology in Medical Sciences Nanotechnology-enabled medicines, called nanomedicines by some authors, have brought about significant progress in the treatment of many diseases. Nanomedicines include a wide range of main therapeutic agents, drug delivery carriers and regenerative medicines, which are more effective than conventional medicines and/or have less side effects. In addition to these pharmaceutical productions, nanotechnology has been applied in different sub-areas of medicine like diagnostics, in vivo monitoring, microsurgery, production of better surgical instruments and other medical equipment, etc. This subsection gives the reader some preliminary ideas on these applications. Boisseau and Loubaton (2011), Emerich and Thanos (2003), Salata (2004), etc. may be consulted for detailed discussions on this subject. (a) Production of more effective drugs: Nanostructures and nanoparticles can be used either as one of the major constituents of the medicine or as the drug delivery carriers. The drug delivery systems produced from nanomaterials enable better movement of the drugs in the human body, i.e., they have better pharmacokinetic properties. They also have more accurate targeting properties, administering the drugs to the desired organs or tissues only (Baran et al. 2002; Cascone et al. 2002; Duncan 2003; Kipp 2004). (b) In vitro and in vivo diagnostics: Pathological studies on the nanoscale level, including in vitro and in vivo investigations and imaging, provide a better understanding of the types of the diseases and their origins. The conventional techniques for analyses of blood, urine or tissue samples are time-consuming and laborious works. In some cases, these prolonged procedures cause alteration of samples, thus giving imprecise results. In an emergency situation, the delay in obtaining the results may even seriously impede the treatment of patients. Nanotechnology helps to produce a new range of analytical devices or appliances for pathological analyses that have the following advantages (after https://www.azonano.com/article.aspx?ArticleID=1701). (i)

(ii)

(iii) (iv)

(v)

The size of the analytical devices could be reduced to a great extent. It is even possible to design devices that are small enough to be implanted inside the human body, to facilitate in vivo diagnostics. Nanotechnology has been applied for designing multipurpose analytical devices that are capable of performing more than one pathological function. Such devices are faster, thus preventing sample deterioration and increasing the precision of the tests. The smaller devices need smaller quantities of samples. This makes the sample extraction process easier for the pathologists and less painful for the patients. They give more reliable results from less number of measurements, and in many cases are more cost effective than the conventional techniques.

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(c) Applications in surgeries: Certain inventions in nanotechnology have paved the way for significant progress in microsurgeries, some of which are listed below (after Mali 2013). (i)

Nanotechnology has enabled the invention of less invasive techniques for surgeries that have considerably reduced the trauma and shortened the recovery period of the patients. These techniques are also much faster, less expensive, and reduce the chance of infections in post-operative periods. (ii) Small devices known as biosensors can be designed by nanotechnology, which uses biological molecules like enzymes or antibodies, to detect the presence of certain chemicals. (iii) Nanotechnology has made the surgeons equip with a whole range of new, improved instruments, like nano-coated surgical blades, nano-needles, catheters for minimally invasive surgery, nanocoated or nanocontoured implant surfaces, etc. Nanoparticles of hydroxyapatite can be used as bone cement with better mechanical properties. For detailed descriptions of all these surgical equipment, Mali (2013) may be referred.

7.2.2 Properties of Nanomaterials Favourable for Their Medical Applications Many properties of nanoparticles differ widely from those of the same material on a larger scale, which makes them most suitable for all the medical applications mentioned above in Sect. 7.2.1. A brief explanation of these properties has been given here (after Boisseau and Loubaton 2011). (a) Smaller a particle, larger is its surface area/volume ratio. Owing to the extremely small size of the nanoparticles, their area/volume ratio is very high compared to the larger particles. This extraordinarily high surface area makes them preferable for medical applications for the following reasons: (i) Larger surface area facilitates better chemical interactions with biomolecules. (ii) The reaction time decreases significantly with the particle size of reactants, i.e., smaller the reactant particles, the less the reaction time. As a result, the chemical and biochemical reactions are much faster when nanomaterial reactants are involved. This enables the production of more efficient and sensitive analytical devices. (b) It has been mentioned earlier that nanotechnology facilitated the reduction of the size of many analytical devices. This has been made possible by using nano pillars or nano beads the sensing part of those devices. This enables the production of minute analytical devices, which have the following advantages.

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(i) The miniature devices can be used more efficiently. If required, they can be implanted easily within the human body, which is not possible with larger devices. (ii) The analytical device with very small sensing parts requires a very small quantity of biological samples for the detection of disease. This is very useful for some analytical tests like biopsies.

7.2.3 Basic Ideas on Clay Nanocomposites and Nanohybrids Nanoclays may be defined as nanoparticles of layered mineral silicates consisting of an extremely thin layer of 1 nm thickness with exceptional mechanical properties (modified after Huang 2018). It may be mentioned here that Huang (2018) has used the word “two-dimensional” in the definition of nano clay, and many other authors have also described some nanoclays to be two-dimensional. But all the real materials are actually three-dimensional, however thin they may be. Nanoclays may be formed by natural processes of weathering and sedimentation, and also can be produced artificially. Montmorillonite is the most common mineral species of natural nanoclay. Natural bentonites may contain 60–80% of extra-fine montmorillonite nanoparticles produced by the natural weathering of volcanic ash, tuffs, and basic rocks. Allophane, another natural nanomaterial, is a non-crystalline aluminosilicate derived from the weathering of volcanic ash. Being non-crystalline, however, it does not qualify as a mineral. Therefore we do not prefer to call it a nanoclay. The soil in the areas surrounding active or dormant volcanoes is largely derived from weathering of volcanic ash, and the inorganic fraction of such soil is dominated by nanomaterials like montmorillonite and allophane. It may be noted that the nanoparticles derived from some phyllosilicates other than clay minerals, like micas, serpentines, talc, etc., are also considered as nanoclays by some authors (Floody et al. 2009; Nanografi 2019). The unique structures and properties of nanoclays, along with their ability to combine with other substances, facilitate the production of a wide variety of nanomaterials from them. Many of these nano-structured material composites are synthesised by combining pure clay minerals with some inorganic or organic materials, through electrostatic interactions or covalent bonding. These material composites are called nanocomposites of clay minerals or clay nanocomposites if at least one of their constituents, i.e., the clay or the other material, has dimensions in the nanometer regime, i.e., between 1 and 100 nm (after Harraz 2019). For many industries, especially the food preservation industries, a definite category of clay nanocomposites is produced by combining different types of polymers with nanoclays, which are known as Polymer–Clay Nanocomposites or PCN (See Sect. 7.2.4 of this chapter for further discussions on this subject). The PCNs are normally produced by the following three methods (after Brody et al. 2008; Ray et al. 2006). (a) Solution method: This method involves the addition of a solvent to the nanoclay, which causes the interlayer space of nanoclay to expand. The swollen mass of

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nanoclay thus produced is then added to a solution of a suitable polymer, which causes the polymer molecules to extend between the layers of clay. Then the solvent is evaporated. (b) In situ polymerisation technique: In this method, the clay nanoparticles are swollen by the absorption of a liquid monomer (a molecule that bonds with other identical molecules to form a polymer). After the monomer penetrates the interlayer spaces of the clay, polymerisation is initiated by heat, radiation, or the incorporation of an initiator. (c) Melt processing: This is the most common method for the synthesis of PCNs. The polymers are used in the molten state, thus no solvents are required in this process. The nanoparticles of montmorillonite are incorporated into a molten polymer, from which the final material is produced. Nanohybrids, in contrast to nanocomposites, are the combination of two different nanomaterials by chemical bonding. Several types of nanohybrids can be produced by combining clay minerals with drugs at the nanoscale level, which are known as clay-drug nanohybrids. In this chapter, we have used the term nanoclay derivatives for both clay nanocomposites and clay-drug nanohybrids. The inherent therapeutic properties of clay minerals may be substantially enhanced in the nanoclay derivatives. The highly effective antimicrobial and antitoxic properties of these materials have wide-ranging applications in the pharmaceutical industries and food preservation industries, some of which have been described in Sects. 7.2.4 and 7.2.5, respectively.

7.2.4 Nanoclay Derivatives in Pharmaceutical Industries (a) Nanoclays as the main ingredients of medicines: Some therapeutic properties of clay minerals are enhanced in the clay nanoparticles, due to their extremely small sizes. They also have some novel antimicrobial and antitoxic properties, which make them very useful in the pharmaceutical industry. Furthermore, some tailor-made drugs may be synthesised by combining nanoclays with other nanomaterials. Abduljauwad et al. (2020) suggested that the cohesive energy densities of nanoclays are very high, which makes them suitable for the production of antiviral drugs that can be effective against COVID-19 (detailed description is given in Chap. 6, Sect. 6.4). (b) Nanoclay-based drug delivery systems: The nanoclays can regulate effectively the diffusion coefficient, concentration gradient, and distribution coefficient of the drug molecules associated with them. These attributes make them very much suitable for the manufacture of drug delivery systems. A comprehensive explanation of drug delivery systems and the applications of clays in their production has been given in Chap. 6, Sect. 6.4.3.

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The drug delivery systems composed of nanoclays, in addition to effectively controlling the rate, time and place of the release of drug molecules, can greatly enhance the effectiveness of some drugs. Some mesoporous nanomaterials, characterised by nano-sized porosities, can be produced from clay minerals (such as kaolinite, hectorite, etc.) or their synthetic derivatives, which are found to be very effective to produce repurposed anti-COVID-19 drugs (Piao et al. 2021; Teodorescu and Morariu 2022). A detailed explanation of this application of nanoclays has been given in Chap. 6, Sect. 6.4.3(b). For a comprehensive review on the application of nanoclays as drug carriers, Gaharwar et al. (2019) may be consulted. (c) Nanoclay as the carrier of anticancer medicines: Nanoclays are reported to be successfully used in the delivery systems of some anticancer drugs also. Very important pharmaceutical attributes have been observed in curcumin, a natural polyphenol derived from the rhizome of the plant Curcuma longa, which can be effectively utilised in the treatment of cancer. The antioxidant and anticancer medications derived from it are believed to have less side effects than many other anticancer drugs and were found to be safe even in high doses. But it has two serious shortcomings. First, its solubility in water is too low to be used effectively in medicine. Second, it has low bioavailability, i.e., a very small proportion of orally administered curcumin enters the circulation, and actively participates in the treatment of diseased cells. Dionisi et al. (2015) reported that a drug delivery system composed of halloysite clay nanotubes can be effectively used for curcumin delivery to cancer cells. These halloysite nanotubes, prepared from natural halloysites, have an average inner diameter of ~15 nm and length of 1000 nm. The major advantages of the drug delivery system produced from halloysite nanotubes are: (i)

The loading procedure of curcumin in the halloysite nanotube is easy and simple. (ii) Halloysite nanotube enables constant and slow release of curcumin to the cancer cells. The drug release may be further controlled by using claypolymer nanocomposites, in which the external surfaces of the nanotubes are covered by layers of two polymers: poly-L-lysine and poly-acrylic acid. (iii) This drug carrier is not expensive, since its main constituent is the naturally occurring, easily available halloysite. (d) Expected dual antimicrobial actions of drugs composed of nanoclays: The nanoclays have some actions of their own against certain groups of microbes, like the spiked viruses. In addition, they can increase the effectiveness of the other antimicrobial medicines when used as drug carriers. It is, therefore, expected that new clay-based nanocomposites may be synthesized by combining clays with other drugs, which will utilise both therapeutic properties of the nanoclays. Such novel formulations are expected to produce more effective antimicrobial agents. This has been explained in Chap. 6, Sect. 6.4.4, and schematically shown in Fig. 6.8.

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(e) Nanoclays in regenerative medicines: These medicines help in the replacement, engineering, or regeneration of human or animal cells, tissues or organs, to restore their normal functions. The most important function of regenerative medicines is tissue engineering, i.e., restoration or improvement of damaged tissues or whole organs, along with prevention of infection and minimisation of the immune response. The applications of nanotechnology have brought about significant progress in the field of tissue engineering. Regeneration of tissues can be highly enhanced on almost any surface by employing nano-textured surface features. A large number of studies have reported that nanotechnology accelerates various regenerative therapies for the tissues of bone, cartilage, heart, bladder and brain. (Engel et al. 2008; Khang et al. 2010; NIH fact sheets 2006; Solanki et al. 2008). Laponite nanoclay, trioctahedral smectite, has attributes that can be utilised to control cell functions for tissue engineering. A detailed review of the applications of laponite and other nanoclays in regenerative medicines is given by Gaharwar et al. (2019). (f) Taste masking of drugs by nanoclay derivatives: Taste masking is the reduction of the unpleasant taste of a substance that would otherwise exist (Sohi et al. 2004). This can be done by inhibiting the contact of those substances with the taste buds of the human tongue. Many drugs have undesirable tastes, which must be masked or blocked when they are administered orally. A number of nanohybrids synthesised by combining clay nanoparticles with drug nanomaterials, such as aripiprazole + montmorillonite, sildenafil + montmorillonite, etc. can be used for this purpose.

7.2.5 Nanoclay Derivatives in Food Preservation and Packaging The antimicrobial and antitoxic properties of the clay minerals, as have been discussed in this book, are largely utilised in the preparation of therapeutic agents. It has also been mentioned that these properties may be applied in the purification of water, soil, etc. as well. Since the late 1990s, however, the advancement of nanotechnology has initiated the application of the antimicrobial properties of nanoclays in an entirely new field—the food preservation and packaging industries. An outline of the application of clay nanocomposites in this field is given here. In the present age, industrially processed instant foods and semi-cooked foods are preferred over conventional raw food materials by a huge population throughout the world. Extensive research is going on to determine some effective ways for food preservation and food packaging, which must satisfy the following criteria: (i)

The foods must be protected from microbial decomposition for a certain time, which will increase their shelf lives. (ii) Their nutritional values must be preserved also. (iii) Their taste and flavour must not deteriorate by prolonged preservation. (iv) The preservatives must not be harmful to human health in any respect. Many common chemical antimicrobial agents used for food preservation fail this criterion.

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With the advent of nanotechnology, it has been possible to preserve a wide range of food materials by synthesising an equally wide variety of nanomaterials. Grumezescu (2017) may be consulted for a comprehensive review of the latest food preservation techniques. A large number of natural or synthetic antimicrobial agents have been formulated that can control the microbial contamination of foods and extend their shelf lives; without any detrimental effects on human health. Some of the most effective ones among them are nanocomposites of clays, produced by combining nanoclays with different types of polymers. The nanoclays have some inherent antimicrobial properties of their own. In addition, they can encapsulate other antimicrobial agents and release them by controlled diffusion. The latter attribute of nanoclays is comparable to that of a clay-based drug carrier that enables the targeted and controlled release of drugs. As early as the 1990s, a wide variety of Polymer–Clay Nanocomposites (PCN) were produced by combining montmorillonite with different types of synthetic polymers (such as polyethylene, Nylon, Poly Vinyl Chloride etc.) and biopolymers (like starch, cellulose etc.). As defined in Sect. 7.2.3 of this chapter, one of the constituents of a nanocomposite must be in nanoscale. In these PCNs, the nanocomponent was montmorillonite nanoparticles (commonly 1–5% by weight) with a layer thickness in nanometer dimension (~1 nm). The length and width of these extremely thin sheet-like nanoparticles were in the range of a few micrometers. Their aspect ratios were, therefore, considerably high, i.e., greater than several thousand. The interlayer cations of these nanoclays were replaced with lithium and sodium (Lange and Wyser 2003; Ray et al. 2006). Three common methods for the preparation of these PCNs have been described in Sect. 7.2.3. The PCNs have the following properties that make them more suitable in the food packaging industries than the other materials: (i) (ii) (iii) (iv) (v) (vi)

Greater imperviousness against microbes, oxygen, carbon dioxide, and moisture, prevented microbial action in the foods packed within them. Less penetration of ultraviolet rays, which prevented food degradation. Prevention of the escape of volatiles from foods and beverages, which helped to preserve their flavours and tastes. Superior mechanical strength. Reduction in weight. More heat-resistant and flame retardant than the other packaging materials.

7.3 Potential Environmental Hazards of Clay-based Medicinal Industries The airborne particulate matters (PM) or suspended particulate matter (SPM), which are very fine (microscopic or submicroscopic) solid particles or liquid droplets dispersed through the air and caused severe air pollution in the industrial areas. The inhalable particulate matters, which can enter the human respiratory system

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through inhalation, are broadly divided into two groups: the inhalable coarse particles or PM10 , having diameters less than 10 µm; and the inhalable fine particles or PM2.5 , which are finer particles with diameter of 2.5 µm or less (U.S. Environmental Protection Agency 2021). The sources and types of both PM10 and PM2.5 are many and varied, including the minerals derived from the natural or industrial sources such as quartz, feldspars, chlorite, clay minerals (kaolinites, illites, and smectites being most abundant), and carbonates; and the oxides iron, aluminium, and manganese. The major non-mineral components of PM are the fine carbon particles from furnaces, boilers, and automobile emissions, inorganic colloidal oxides, organic materials like humic substances and polysaccharides, microbes, etc. Many types of PM, especially PM2.5 , can reach deep inside the human respiratory systems, enter the human lungs and cause respiratory diseases (Fitzsimons 2011; Kuwata and Nishikawa 2005). The airborne particles of clay minerals, present as both PM2.5 and PM10 , are derived from the natural sources like soil, exposed clay layers, etc., and the anthropogenic sources such as clay mines, the overburden dumping sites of all types of mines, the beneficiation plants and manufacturing units of clay-based industries, etc. The entry of PM into the respiratory systems of humans and animals can cause a wide variety of respiratory diseases (like asthma, lung cancer) and cardiovascular diseases, some of which may even lead to premature death. PM2.5 alone accounts for more than four million death worldwide each year. The other diseases commonly attributed to PM are premature delivery, birth defects, low birth weight, developmental disorders, neurodegenerative disorders, mental disorders, etc. (Braithwaite et al. 2019; Chun et al. 2020; Flores-Pajot et al. 2016; Fu and Yung 2020; Lam et al. 2016; Lu 2020; Liu et al. 2021; Tsai et al. 2019; Weisskopf et al. 2015). As long as the clays were used in the traditional ways, a small amount of it was extracted from nature, purified, and the desired therapeutic agents were prepared. The number of particulate matter produced in this process was so small that it did not cause any significant pollution of the air, even on a local scale. But with the advent of modern civilisation, the gradually increasing demands for different clay products brought about an enormous increase in the use of clays in the industries. This has led to the release of considerable quantities of fine or ultrafine particles of clays during all the stages of industrial production—from mining, and beneficiation to the final manufacturing processes. In most cases, the natural clays are extracted from surface mines (open cast or open pit mines). The layers of clays exposed in these mines are also the major contributors to the airborne fine particles of clays, especially in dry conditions. A sprinkling of a sufficient amount of water in the extraction zones and waste dumps of these mines may help to alleviate this problem. The potential health and environmental issues arising from the clay-based industries are briefly described below. (a) Adverse effects on human health: The harmful impacts of inhalation of clay minerals, and the pathological consequences of excessive exposure of the human respiratory system to the airborne dust particles have been established in several

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studies. Inhalation of sufficient quantities of montmorillonite, kaolinite, and associated mica flakes was reported to cause chronic bronchitis. People with prolonged exposures to these minerals may develop symptoms of pneumoconiosis, an interstitial lung disease causing lots of coughs, phlegm, and shortness of breath. Some clay minerals like vermiculites are associated with the grains of amphibole asbestos, which may enter the lungs through respiration and cause lungs cancer (Gibbs 1990; Gibbs et al. 1992; Gibbs and Pooley 1994; Wagner 1990; Wagner et al. 1987, 1998). The workers associated with the clay-based industries, and the people residing in the immediate vicinity of the clay mines or production plants are the immediate sufferers of the clay–induced air pollution. However, Wagner et al. (1998) opined that the vast majority of airborne clay particles are not harmful, and can only bring about respiratory disorders if the exposure is intense and continues for a long period of time. (b) Impacts on the water resources: In addition to the health issues of people in the surrounding areas, clay particles released from the clay mines and factories sometimes settle in the water bodies and make the water turbid. This may make the water unsuitable for drinking and other uses. An increase in turbidity of water may also have adverse effects on all the aquatic life forms. In some extreme cases, the deposition of too much clay particles in the surface water bodies may choke or fill up the small ponds or lakes. This may also affect the flows of running water, and change the course of small streams or rivers. It may be noted here that, the factories of clay-based pharmaceuticals generally release considerably less amounts of PM10 or PM2.5 in the air than the other industries where much greater quantities of clays are used, like the porcelain factories, manufacturing plants of refractory bricks and cements, etc. Furthermore, it is not very difficult to deal with clay-induced health problems and environmental degradation. Some simple remedial measures like the proper use of sprinklers at all the possible sources of pollution, use of suitable face masks for the workers, appropriate management of waste disposal sites of the factories, etc. will help to mitigate such problems to a large extent.

7.4 Suggested Fields for Future Investigations Of all the hazards that can endanger the existence of human beings on the face of Earth, the most perilous ones are possibly the pathogenic microbes that cause widespread infections. The natural and anthropogenic toxins also feature among the potential threats that can bring about irreparable damage to human health, and long-lasting degradation of nature. As we have shown in this book, clay is one of the very few effective and trustworthy substances that have enabled the human civilisation to ward off these menaces since time immemorial. However, the microbes are always capable of mutating into more virulent strains that cannot be dealt with the

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older therapeutics; and the rapid advent of industrialisation is introducing new, more harmful toxins in larger quantities to the soil, water, and air. Such a situation calls for the formulation of new, improved medications, which are capable of destroying or removing the microbes and toxins without affecting human health. As explained comprehensively in Sect. 7.1, the clay minerals are very much appropriate for this purpose. However, the synthesis of more effective clay-based medicines, tailor-made for the treatment of certain infectious diseases or toxicosis, requires an integrated effort of specialist researchers from various disciplines. This section points out some of the fields of investigation that may help to achieve this goal in the future.

7.4.1 Mineralogical and Material Scientific Researches It has been well emphasised throughout our discussions that, all the antitoxic and antimicrobial applications of the clay minerals are based on their internal structures and compositions, and the consequent physical and chemical properties that are unique to these minerals. A better understanding of the structures, compositions, and properties of these minerals will therefore help in the diversification of their applications and also in the production of new substances with desired therapeutic qualities. The researchers should especially concentrate on the study of the cation exchange capacity, sorption coefficient and other properties of clay minerals that are important in their antimicrobial and antitoxic applications. The following aspects should be taken into consideration in such investigations: (a) Variation of properties among different groups and different species: It is required to study the variation of the above properties, as a function of structure and chemical composition, among the different clay mineral groups, and also among the different species within a group. (b) Properties of different types of clay composites: The properties of a clay mineral species may be enhanced or diminished by the introduction of different organic and inorganic molecules in its structure. If such variations of properties are studied meticulously and recorded, that may help to formulate new clay derivatives with the desired attributes. Studying the properties of different homoionic varieties of the same clay mineral species may be useful in this regard. (c) Change of behaviour in different physico-chemical environments: The physical and chemical conditions vary widely within the different organs or parts of organs in the human body. For example, within the gastro-intestinal tract of humans and many other animals, the pH is highly acidic in the stomach and alkaline in the small intestines. There may be significant variations in the cation exchange capacity, sorption coefficient and other properties of clay minerals in such widely varying chemical environments.

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The clays are generally nontoxic to the human body. But in certain physicochemical environments, it may not be impossible for some clay minerals or their organic or inorganic composites to develop some amount of toxicity. It is, therefore, important to study the variation of properties of clay minerals and their products in different environments. In vitro investigations may be performed by simulating such conditions in the laboratory, and any changes in the behaviour of clay minerals in those conditions must be recorded. This may help in the production of specialised clay-based medicines that will act within a certain organ of the human body, and lessen the side effects of these medicines. Similar investigations may also be carried out by simulating the physical and chemical conditions of some abiogenic systems, such as in a toxic waste disposal tank of a chemical factory, etc. This will be useful for the synthesis of more effective clay-based substances for environmental protection.

7.4.2 Pathogenic and Microbiological Investigations As explained in Chap. 2, Sect. 2.1, the clay minerals cannot destroy the viruses, but remove them from an aqueous system by the following sequence of processes: (i) Adsorption: The very fine clay particles adsorb the viruses on their surfaces. (ii) Flocculation: The clay particles with adsorbed viruses form coagulates or flocs in presence of electrolytes in an aqueous medium. (iii) Removal: The flocs, being heavier than the aqueous medium, are slowly removed from the system through decantation or other processes. This indicates that the antiviral actions of clays depend largely on their adsorptive power, and the clays with greater flocculation power may remove the viruses more rapidly from a system. A wider and more effective application of the antiviral properties of clays, therefore, requires a better understanding of these processes, and further investigations in the following fields may be recommended to achieve that. (a) Identification of the clay mineral most suitable for removal of a particular virus: The ability of different clay minerals to adsorb a certain virus varies significantly. Similarly, a clay mineral interacts differently with different types of viruses. Most of the workers have studied so far the adsorption of one or two types of viruses by a particular type of clay. For example, Sykes and Williams (1978) studied the adsorption of actinophage f6 virus by kaolinite; Schaub and Sagik (1975) studied the actions of montmorillonite on two encephalomyocarditis viruses, etc. A number of similar studies on virus adsorption carried out so far have been described in Chap. 2, Sect. 2.1. But the production of more effective, virus-specific drugs from the clay minerals requires a much larger database on virus-clay interactions, which requires further studies on the adsorption of a wider range of viruses by different types of clay minerals. This will enable future pharmacologists to identify the clay mineral species that will most effectively adsorb a certain kind of virus.

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(b) Detection of the controlling factors of the adsorption process: The preparation of more effective clay-based antiviral drugs necessitates the identification of different physical, chemical and biological factors that can have positive or negative impacts on the virus adsorption process of clay minerals. Especially, the effects of cations and their comparative efficiency in the adsorption process require to be reassessed by further studies. A wide variety of homoionic clays may be produced by combining different clay mineral species with different cations, and their interactions with a particular type of virus can be recorded. The database thus produced will help to identify the most effective combination for the adsorption of a particular type of virus. The importance of the CEC of clays in virus adsorption is not yet fully understood, and the contrasting views of different scientists in this regard are explained in Sect. 2.1.3 of Chap. 2. Technological advancements over the last couple of decades have empowered the present researchers with more powerful and accurate tools, which can be utilised to settle these contradictions. (c) Studies on the enhancement of flocculation power: Along with identifying the type of clay (or clay-cation combination) that is most efficient in the adsorption of a particular type of virus, the scientists should also focus on increasing the rate of flocculation of that clay for the easier and faster removal of the virus from the system. Like adsorption, the flocculation rate is also influenced by the concentration and types of cations present in the system; and the identification of the most appropriate cations for accelerating this rate requires further research on this subject. (d) Studies on the adsorption of bacteria by clay particles: The clays can cause the destruction of some bacteria, in presence of Fe2+ , by a series of chemical reactions. Most clay-based antibacterial therapeutic formulations utilise this property. But some clays can also adsorb a number of bacteria, especially the smaller forms, and remove them from a system like the viruses. It is, therefore, highly probable that more versatile antibacterial agents can be produced from the clays, to protect us from a wider range of bacteria, if their adsorptive properties are further explored and utilised by future researchers.

7.4.3 Chemical and Biochemical Investigations For better utilisation of the therapeutic properties of clay minerals, it is very important to have a clear understanding of the chemical reactions that are associated with their antibacterial, antiviral and antitoxic actions. The present state of knowledge on the mechanisms of these reactions of clay minerals has been explained in Chap. 2, from which some lacunas of the chemical and biochemical studies in this field may be identified. Clays support the bactericidal actions of some metals, and some of the associated reactions are enhanced in an aquatic system in presence of clay minerals. Fe2+ is found to be the most effective bactericidal metal, which can destroy a wide variety

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of bacteria, including Escherichia coli, Mycobacterium marinum, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella enterica, Salmonella aureus, Serovar typhimurium, and Staphylococcus aureus (Cunningham et al. 2010; Haydel et al. 2008). The excess concentration of Al3+ along with Fe2+ into the destroyed bacteria cells suggests that Al3+ may also be associated with the bactericidal reactions. Based on the present state of knowledge, a brief explanation of these reactions has been given in Chap. 2, Sect. 2.2.1. But our knowledge of these reactions, and the role of clay minerals in these, are far from complete. A few areas for future research in this field are suggested below. (a) Actions of different metals on a particular bacteria: The clay-supported bactericidal actions of Fe2+ have been widely studied. Similar investigations should be carried out in presence of clay with other metals, especially zinc, copper, etc. which have well-known bactericidal attributes, and the reaction mechanisms in each case must be studied carefully. This will help to identify the metal that is most suitable to destroy a particular bacteria. (b) Identification of the most appropriate clay mineral in the bactericidal action of metal: The clay minerals are believed to have dual roles in the bactericidal actions of metals: firstly, they act as the source of that metal, and secondly, they act as a buffer in these reactions. Keeping the bacteria and the metal constant, these tests may be performed in presence of different types of clay minerals. Different types of homoionic clays may also be used in such studies. This will help to identify the most effective clay mineral or homoionic clay to destroy a particular bacteria. (c) Bactericidal reactions in different environments: The bactericidal actions of metal may vary significantly in different physical and chemical environments; for example, within the different parts of human or animal gastro-intestinal tracts, in a toxic waste disposal tank of a chemical factory, etc. In vitro investigations may be performed by simulating such conditions in the laboratory, and the change in the behaviour of clay minerals can be studied.

7.4.4 Researches on Nanoclays and Nanoclay Derivatives It is clear from all the instances given in Sect. 7.2.4 that, further investigations on different facets of the nanoclays and clay-drug nanohybrids may open new horizons in the pharmaceutical industries. Synthesis of new nanomaterials by combining clays with other organic and inorganic substances, and meticulous studies of their physical, chemical and pharmacological properties may facilitate the formulation of novel therapeutic agents with greater efficacies against microbes and toxins. The necessity for further research on nanoclay-based medicines is therefore highly recommended. Special emphasis may be given to the utilisation of the enhanced antimicrobial and drug carrier properties of nanoclays, which is expected to help in the following regard:

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(i) Production of more effective and versatile ‘clays-alone’ antimicrobial drugs (ii) More successful treatment of infectious diseases by the synergistic antimicrobial effects of nanoclay-based drug carriers and the antibiotic agents loaded into them (See Sect. 6.4.4 of Chap. 6 for a brief discussion on this matter) (iii) Production of better anticancer drugs, with less side effects, by encapsulation of highly toxic anticancer substances inside clay nanotubes, as exemplified in Sect. 7.2.4(c).

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Liu, G., Song, Y., Wang, J., Zhuang, H., Ma, L., Li, C., Liu, Y. and J. Zhang (2014). Effects of nanoclay type on the physical and antimicrobial properties of PVOH-based nanocomposite films. LWT – Food Sci. Technol., 57: 562–568. Liu, Q., Wang, W., Gu, X., Deng, F., Wang, X., Lin, H., Guo, X. and S. Wu (2021). Association between particulate matter air pollution and risk of depression and suicide: A systematic review and meta-analysis. Environmental Science and Pollution Research, 28(8): 9029–9049. https:// doi.org/10.1007/s11356-021-12357-3 Lu, J.G. (2020). Air pollution: A systematic review of its psychological, economic, and social effects. Current Opinion in Psychology, 32: 52–65. https://doi.org/10.1016/j.copsyc.2019.06.024 Mackay, M.E., Tuteja, A., Duxbury, P.M., Hawker, C.J., Van Horn, B., Guan, Z.B., Chen, G.H. and R.S. Krishnan (2006). General strategies for nanoparticle dispersion. Science, 311: 1740–1743. Mali, S. (2013). Nanotechnology for surgeons. The Indian Journal of Surgery, 75(6): 485–492. https://doi.org/10.1007/s12262-012-0726-y Mascheroni, E., Chalier, P., Gontard, N. and E. Gastaldi (2010). Designing of awheatgluten/montmorillonite based system as carvacrol carrier: Rheological and structural properties. Food Hydrocoll., 24: 406–413. Meira, S.M.M., Jardim, A.I. and A. Brandelli (2015). Adsorption of nisin and pediocin on nanoclays. Food Chem., 188: 161–169. Mukherjee, S. (2013). The science of clays. Springer. ISBN: 978-93-81891-03-2. Nanotechnology improving healthcare through in vitro biosensors and integrated devices and invivo implantable devices and medical imaging, AZo-Nanotechnology Article, http://www.azo nano.com/Details.asp?ArticleID=1701#_In-vitro_Diagnostics. Nunes, C.D., Vaz, P.D., Fernandes, A.C., Ferreira, P., Romão, C.C. and M.J. Calhorda (2007). Loading and delivery of sertraline using inorganic micro and mesoporous materials. Eur. J. Pharm. Biopharm., 66: 357–365. Owens, B. (2015). Pharmaceutical in the environment: A growing problem. The Pharmaceutical Journal, 294: 7850. https://doi.org/10.1211/PJ.2015.20067898 Pautrat, J. (2011). Nanosciences: Evolution or revolution? Comptes Rendus Physique, 12(7): 605– 613. https://doi.org/10.1016/j.crhy.2011.06.003 Pereira De Abreu, D.A., Paseiro Losada, P., Angulo, I. and J.M. Cruz (2007). Development of new polyolefin films with nanoclays for application in foodpackaging. Eur. Polym. J., 43: 2229–2243. Piao, H., Rejinold, N.S., Choi, G., Pei, R., Jin, G. and J. Choy (2021). Niclosamide encapsulated in mesoporous silica and geopolymer: A potential oral formulation for COVID-19. Microporous and Mesoporous Materials, 326: 111394. https://doi.org/10.1016/j.micromeso.2021.111394 Ray, S., Easteal, A., Quek, S.Y. and X.D. Chen (2006). The potential use of polymer-clay nanocomposites in food packaging. Int J Food Eng, 2(4): 1–11. Regenerative medicine, NIH fact sheets (2006). http://www.nih.gov/about/researchresultsforthepub lic/Regen.pdf. Report: The appropriateness of existing methodologies to assess the potential risks associated with engineered and adventitious products of nanotechnologies. (2006). Scientific committee on emerging and newly identified health risks (SCENIHR) (during the 10th plenary meeting of 10 March 2006 after public consultation) pp. 1–79. Synthesis report : http://ec.europa.eu/health/ ph_risk/documents/synth_report.pdf. Rhim, J.W., Hong, S.I. and C.S. Ha (2009). Tensile, water vapor barrier and antimicrobial properties of PLA/nanoclay composite films. LWT – Food Sci. Technol., 42: 612–617. Rodrigues, L.A.D.S., Figueiras, A., Veiga, F., De Freitas, R.M., Nunes, L. C.C., Da Silva Filho, E.C. and C.M. da Silva Leite (2013). The systems containing clays and clay minerals from modified drug release: A review. Colloids Surf. B Biointerfaces, 103: 642–651. Salata, O.V. (2004). Applications of nanoparticles in biology and medicine. J. Nanobiotechnology, 2: 3. Sanchez-Garcia, M.D., Ocio, M.J., Gimenez, E. and J.M. Lagaron (2008). Novel poly-caprolactone nanocomposites containing thymol of interest in antimicrobial film and coating applications. J. Plast. Film Sheet, 24: 239–251.

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Savas, L.A. and M. Hancer (2015). Montmorillonite reinforced polymer nanocomposite antibacterial film. Appl. Clay Sci., 108: 40–44. Shemesh, R., Krepker, M., Goldman, D., Danin-Poleg, Y., Kashi, Y., Nitzan, N., Vaxman, A. and E. Segal (2015). Antibacterial and antifungal LDPE films for active packaging. Polym. Advan. Technol., 26: 110–116. Silvestre, C., Duraccio, D. and S. Cimmino (2011). Food packaging based on polymernanomaterials. Prog. Polym. Sci., 36: 1766–1782. Sinha, R.A.Y., Okamoto, S. and K.M. Okamoto (2003). Structure–property relationship in biodegradable poly (butylene succinate)/layered silicate nanocomposites. Macromolecules, 36: 2355–2367. Sohi, H., Sultan, Y. and R.K. Khar (2004). Taste masking technologies in oral pharmaceuticals: Recent developments and approaches. Drug Development and Industrial Pharmacy, 30(05): 429–448. https://doi.org/10.1081/DDC-120037477 Solanki, A., Kim, J.D. and K. Lee (2008). Nanotechnology for regenerative medicine: Nanomaterials for stem cells imaging. Nano medicine, 3(4): 567–578. Teodorescu, M. and S. Morariu (2022). Drug delivery system based on PVA and clay for potential treatment of COVID-19. Journal of Polymer Research, 29: 67. https://doi.org/10.1007/s10965022-02927-5 Tsai, T.L., Lin, Y.T., Hwang, B.F., Nakayama, S.F. Tsai, C.H., Sun, X.L., Ma, C. and C.R. Jung (2019). Fine particulate matter is a potential determinant of Alzheimer’s disease: A systemic review and meta-analysis. Environmental Research, 177: 108638. https://doi.org/10.1016/j.env res.2019.108638. U.S. Environmental Protection Agency (2021). Policy Statement on Climate Change Adaptation. Washinton, D.C. 20460. Vaia, R.A. and Giannelis, E. P. (1997). Polymer melt intercalation in organically modified layered silicates: Model predictions and experiment. Macromolecules, 30: 8000–8009. Villanova-de-Benavent, C. (2020). Geological overview of clay Nanoparticles. Clay Nanoparticles (Elsevier). pp. 3–36. https://doi.org/10.1016/B978-0-12-816783-0.00001-3. Viseras, C., Cerezo, P., Sanchez, R., Salcedo, I. and C. Aguzzi (2010). Current challenges in clay minerals for drug delivery. Appl. Clay Sci., 48: 291–295. Vladimirov, V., Betchev, C., Vassiliou, A., Papageorgiou, G. and Bikiaris, D. (2006). Dynamic mechanical and morphological studies of isotactic polypropylene/fumed silica nanocomposites with enhanced gas barrier properties. Compos. Sci. Technol. 66: 2935–2944. Wagner, J.C. (1990). Review on pulmonary effects of phyllosilicates after inhalation. In: Bignon, J. (Ed.), Health Related Effects of phyllosilicates. NATO ASI Series, Springer–Verlag, Berlin, G21: 309–318. Wagner, J.C., Grifiths, D.M. and D.E. Munday (1987). Experimental studies with palygorskite dust. British Journal of Industrial Medicine, 44: 749–763. Wagner, J.C., Mc Connochie, K., Gibbs, A.R. and F.D. Pooley (1998). Clay minerals and health. In: Parker, A. and J.E. Rae (Eds.), Environmental Interactions of Clays. Springer–Verlag, Berlin. pp. 243–265. Weiss, J., Takhistov, P. and J. McClements (2006). Functional materials in food nanotechnology. J Food Science, 71(9): 107–116. Weisskopf, M.G., Kioumourtzoglou, M. and A.L. Roberts (2015). Air Pollution and Autism Spectrum Disorders: Causal or Confounded? Current Environmental Health Reports, 2(4): 430–439. https://doi.org/10.1007/s40572-015-0073-9. PMC 4737505 Williams, L.B., Holland, M., Eberl, D.D., Brunet, T. and L. Brunet de Courrsou (2004). Killer clays! Natural antibacterial clay minerals. Mineralogical Society Bulletin, 139: 1–8. Zheng, J.P., Luan, L., Wang, H.Y., Xi, L.F. and K.D. Yao (2007). Study on ibuprofen /montmorillonite intercalation composites as drug release system. Appl. Clay Sci., 36: 297–301.

Think for a While

A collection of questions is given here on the important concepts presented in each chapter of this book. It is advisable for the students to think over these questions and solve them after completion of those chapters. This may help them to understand the subjects clearly. A few research articles are cited in some of the questions. The full references of those articles have been given in the reference list of the respective chapters. The students may need to consult some preliminary level books of physics, chemistry or mineralogy for answering a few questions. Chapter 1 Q.1.1 Q.1.2

Q.1.3

What is meant by a mineral species? How is a certain mineral species differentiated from others? Explain the following statement: “a mineral species has a definite but not necessarily fixed chemical composition”. Consult any standard textbook of mineralogy, and show that the composition of dolomite, a mineral species of carbonate class, can vary within a certain limit. Give an example of a clay mineral also, which does not have a fixed chemical composition. Matters are broadly classified into three categories: elements, compounds and mixtures. The mixtures are of two type: homogeneous and heterogeneous (or inhomogeneous). In which of these categories the following materials belong? (a) A mineral species like quartz, which has the fixed chemical composition SiO2 (b) A mineral species like montmorillonite, whose chemical composition varies within a certain limit. (c) A clay, like bentonite (d) Natural soil (e) Sediments of a river, consisting of clay and silt with some sand particles.

© Capital Publishing Company, New Delhi, India 2023 B. Ghosh and D. Chakraborty, Clay Minerals, https://doi.org/10.1007/978-3-031-22327-3

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Is it justified to use the terms ‘soil’ and ‘clay’ interchangeably? Explain. Why kaolin, china clay and bentonite are considered as clay, but kaolinite (species) and montmorillonite are considered as clay minerals? The artists widely use the following two types of materials for modelling purposes. (a) Polymer clay: A soft, gel-like material composed of polyvinyl chloride and a liquid plasticizer. (b) Plasticine clay: A soft, plastic material made from calcium salts, petroleum jelly and fatty acids.

These two substances are commonly known as ‘modelling clays’, still they are not included in any of the clay mineral groups in Sect. 1.2 Why? Justify your answer. Q.1.7 The mineral species muscovite (common mica or white mica) belongs to the phyllosilicate subclass of silicate class. Like a large number of clay mineral species, it has the t-o-t-c structure. Very fine grains of muscovite occur in many rocks and sediments. Still it is not considered as a clay mineral. Explain with reason. Q.1.8 Very fine grains of quartz and feldspars are present in many types of natural clays. Still these minerals are not considered as clay minerals. Why? If the proportion of these minerals in a clay increases, what would be the possible effects on the properties of that clay? Q.1.9 How would you differentiate between dioctahedral and trioctahedral clay minerals? Explain with relevant diagrams. Q.1.10 Which subclass of silicate class is appropriate for the clay minerals of palygorskite–sepiolite group: inosilicate or phyllosilicate? Explain your answer with reasons and suitable diagrams. Q.1.11 The physical and chemical properties of a mineral depend on their chemical compositions and internal structures. Which possible differences in properties can you predict in between the following phyllosilicate pairs? (a) The phyllosilicates with t-o-t structure and t-o-t-c structure. (b) Colours of dioctahedral and trioctahedral micas. (c) Phyllosilicates with monovalent and divalent interlayer cations. Give suitable examples wherever applicable. Any textbook of mineralogy may be consulted for examples of important phyllosilicate species and their properties. Q.1.12 Describe how the internal structures of the clay minerals of kaolinite group differ from those of smectite and vermiculite groups. State the possible implications of these structural differences on the properties of these minerals. Q.1.13 When hammered, the common silicate minerals like quartz and feldspar are crushed to powder, while the clay minerals break into very fine flakes. Explain how this difference in their properties are related to their structural

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Q.1.15

Q.1.16 Q.1.17 Q.1.18

Q.1.19 Q.1.20 Q.1.21

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differences, with appropriate sketches. The internal structure of quartz is described in any standard textbook of mineralogy. A sphere, a cube, and a square table top of 2 cm thickness have equal volumes of 200,000 cm3 . Arrange them in descending order of specific surface area. Do the particles of clay mineral and quartz have equal specific surface areas? Explain this in terms of their internal structures. Other than the clay minerals, which minerals may have high specific surface areas and why? Why the specific surface area of clay mineral is important in its antimicrobial and antitoxin applications? What are chromophores? How do they affect the colour of minerals? Pure kaolinite is white, but the minerals of vermiculite group are brown, dark red or bronze-coloured. Explain this in terms of their chemical compositions. If you find a brown coloured natural sample of kaolinite, what does that indicate? Why do the t-o-t layers of illites, smectites and vermiculites commonly have a net negative charge? Why are the cation exchange properties of the clay minerals important in the context of this book? What is diadochy or ionic substitution? Is it possible to replace a certain cation by any other type of cation? Explain with suitable examples. It is recommended to consult any standard textbook of mineralogy for the examples. What is meant by the ‘cation exchange capacity’ of a mineral? Deduce the relationship between the two units of cation exchange capacity: milli equivalent/100 g and centimole/kilogram, for monovalent, divalent, and trivalent cations. The mineral species of vermiculite and smectite groups have much greater cation exchange capacities than those of kaolinite group. What is the reason for this? Explain why the illites, in spite of having t-o-t-c structures like vermiculites and smectites, have much less cation exchange capacities. Why is the cation exchange capacity of hydrated halloysite greater than that of pure kaolinite species? Why is the adsorptive property of clay mineral important in the context of this book? Why are the adsorption capacities of clay minerals greater than those of the other common silicate minerals? What is the possible relation between the specific surface area of a given mass of a mineral and its adsorption capacity? What possible relationship can you predict between the cation exchange capacity of a clay mineral and its adsorption capacity? The adsorption of cations by kaolinite increases with increase of pH of the medium. What is the possible reason for this?

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Q.1.31 Explain how the adsorptive properties of the minerals of palygorskite– sepiolite group are related to their internal structures. Q.1.32 The objective of this book is to describe the antimicrobial and antitoxic applications of clay. What is the relevance of the present chapter in this book? Chapter 2 Q.2.1 Q.2.2

Describe adsorption, and explain its differences with absorption. Distinguish between the following pairs of terms: (a) Antimicrobial and Antibacterial (b) Antibacterial and Bactericidal

Q.2.3

Q.2.4 Q.2.5 Q.2.6 Q.2.7

It has been observed that the viruses are not destroyed by adsorption; and they can cause diseases even when adhered strongly to the surface of clay minerals. How is it possible then for the clay minerals to protect human health from viruses? Why Carlson et al. (1968) suggested that inactivation of virus by clay does not involve virus-to-clay electrical attraction? What is the role of cations in the virus adsorption process of the clay minerals? Why do the clay particles suspended in an aquatic medium coagulate in presence of cations? Arrange the following three cations in order of their flocculation powers. (a) Al3+ (b) K+ (c) Ba2+ .

Q.2.8

Q.2.9 Q.2.10 Q.2.11 Q.2.12 Q.2.13

Why these minerals have different flocculation powers? Schaub and Sagik (1975) observed that, virus adsorption during flocculation did not lead to additional removal of virus from suspension. if the previously formed flocs are dispersed again, it can equally adsorb the virus that was introduced later in the system. is there any role of flocculation in the antiviral action of clays? Explain. Why is the cation exchange capacity of a clay mineral important in its virus removal mechanism? What are ‘homoionic’ clay minerals? Why are they important in the study of antimicrobial actions of clay minerals? Why does the kaolinite homoionic to Na+ adsorb greater amounts of viruses than the kaolinite homoionic to Ca2+ or Al3+ ? Why does the montmorillonite homoionic to Na+ show greater adsorption of reovirus than similar quantities of kaolinite homoionic to Na+ ? Lipson and Stotzky (1983) reported relatively low adsorption of kaolinite homoionic to K+ . How can you explain this apparently anomalous result?

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Q.2.14 How do the views of Carlson et al. (1983) differ from those of Lipson and Stotzky (1983) regarding the role of cation exchange capacity in the virus adsorption process by the clay minerals? Q.2.15 Which observation of Lipson and Stotzky (1983), regarding the controlling factors of the virus adsorption process of clay minerals, contradicts the expected result? Express your views in this regard. Q.2.16 What are ‘electrophoretic mobility’ and ‘zeta potential’? How are they related to the virus adsorption mechanism of clay minerals? Q.2.17 Clay minerals have the unique property to expand by incorporation of water in their interlayer spaces. is there any observation to suggest that this property assists in the antibacterial action of clays? Q.2.18 Explain the role of Fe2+ in the synthesis of peroxide compounds inside bacteria cells. Q.2.19 Explain how the peroxide compounds destroy bacteria. Q.2.20 What is a buffer in a chemical system? Describe how the clay minerals act as buffer in aquatic system. Q.2.21 Explain the role(s) of a clay mineral in an aquatic system in the bactericidal action of Fe2+ . Q.2.22 Is it possible for pure kaolinite (species) and illite (species) suspended in a medium of distilled, deionized water to destroy bacteria? Is it true for all the other clay minerals also? Explain with reasons. Q.2.23 The clay minerals rich in Fe2+ can destroy some types of bacteria, but many other Fe2+ containing minerals cannot. How would you explain this? Q.2.24 Describe the bactericidal actions of an associated mineral of clay, and compare it with the bactericidal actions of Fe2+ rich clay minerals. Q.2.25 How does the Fenton reaction help to explain the bactericidal process inside a bacteria cell? Q.2.26 Differentiate between bactericidal and bacteriostatic properties of clay minerals with suitable examples. Q.2.27 The adsorptive properties of clay minerals are most important in their antiviral actions, but not in their antibacterial actions. What is the reason for this? Q.2.28 What are antimicrobial cations? Explain how the clay minerals loaded with such cations can destroy pathogens more effectively. Q.2.29 Why is it inferred that better antibacterial medicines can be produced from copper-loaded vermiculites than copper-loaded smectites? Q.2.30 Many phyllosilicate minerals have t-o-t-c structures like the clay minerals, but they cannot remove the toxins and microbes from a solution. Why? Q.2.31 Briefly discuss how the Helmholtz model differ from the Gouy–Chapman model, and explain how these models help to understand the antitoxic actions of clay minerals. Q.2.32 Explain the model for competitive adsorption of different types of monovalent cations by the clay minerals. Q.2.33 How can you explain the adsorption of monovalent and bivalent organic cations by clay surfaces above their cation exchange capacities?

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Q.2.34 If you want to carry out researches on the production of antimicrobial and antitoxic medicines, how do you think the concepts presented in this chapter are going to help you? Chapter 3 Q.3.1 Q.3.2 Q.3.3 Q.3.4 Q.3.5 Q.3.6

Q.3.7 Q.3.8 Q.3.9 Q.3.10 Q.3.11 Q.3.12 Q.3.13

How do the concepts discussed in this chapter relate to the previous two chapters? Explain. Why the clays have broad-spectrum antimicrobial activity. Compare Kisameet clay with those of the antimicrobial clays described in Chap. 2. Which attributes of the Kisameet clay do you think have made them “therapeutic clay mineral”? What are the advantages of the traditional healing methods involving clays over the conventional industrially synthesized antibiotics? Williams et al. (2008) reported that one type of French Green clay promotes bacterial growth, while another kills bacteria. Explain the difference in the actions of these two types of clays in the treatment of Buruli ulcer. Which properties of clays are responsible for the benefits of peloid therapy? Is there any difference between mud therapy and peloid therapy? How trace element chemistry is related to antimicrobial activity of the clays? How is Pelotherapy applied in Thalassotherapy? Give names of five pathogens against which Kisameet clay works. Give names of two major pathogenic fungi against which Kisameet clay works as antifungal agent. What is ‘flesh-eating’ mycobacterial infection?

Chapter 4 Q.4.1 Q.4.2 Q.4.3 Q.4.4 Q.4.5 Q.4.6 Q.4.7

Q.4.8

Do you think it is necessary to study Chap. 2 before starting this chapter? Explain your views in this regard. Briefly explain the bactericidal applications of smectite and illite. Which one of these two is more effective in the destruction of pathogens and why? Describe after Carretero et al. (2002) the properties of clay minerals that are important in their therapeutic applications. Describe the topical applications of clays in therapeutic and cosmetic purposes. Describe after Cunningham et al. (2010) the broad-spectrum antibacterial activities of natural clay mixtures. Explain the application of sodium rich smectite clay as a laxative, mentioning the properties of that clay which facilitates this application. Explain the application of calcium rich smectite clay as an anti-diarrheal agent, mention the properties of that clay which make it suitable for this purpose. Compare the modern antimicrobial applications of clay minerals with their traditional applications.

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Q.4.9

Why kaolinite, Palygorskite and Sepiolite are used as excipients in pharmaceutical preparations? Q.4.10 How the clay minerals are used as excipients in pharmaceutical preparations? Q.4.11 What is the use of Indomethacin? Q.4.12 What is the role of clay in Fangotherapy? Chapter 5 Q.5.1 Q.5.2

Q.5.3

What are meant by ‘adsorption isotherm’ and ‘adsorption coefficient’? Can you use these terms interchangeably? Explain. If you want to produce a clay-based antitoxic medicine for a given toxin, is it important to know the sorption coefficients of different types of clay minerals in an aqueous solution of that toxin? Give explanation for your answer. The Freundlich sorption coefficient (K f ) for adsorption of a toxin on a clay mineral is measured at different concentration of a toxin in an aqueous medium. What types of adsorption isotherms will be obtained when: (a) K f increases with increase of concentration of a toxin in the medium (b) K f is constant at different concentration of a toxin in the medium (c) K f decreases with increase of concentration of a toxin in the medium

Q.5.4

Q.5.5

Three types of adsorption isotherms can be obtained from the three conditions mentioned in Q.5.3. which one of them is shown in Fig. Q.5.4? give reason for your answer. Draw schematic diagrams for the other two types of adsorption isotherms. What are the main two sources of toxins in the human body?

Fig. Q.5.4 A schematic adsorption isotherm

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Q.5.6 Q.5.7

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Which properties of the clay minerals are related to the removal of toxins from a system? Describe the applications of the clay minerals in the treatment of the following toxin contaminations. (a) (b) (c) (d) (e)

Q.5.8

Q.5.9 Q.5.10 Q.5.11 Q.5.12 Q.5.13 Q.5.14 Q.5.15 Q.5.16 Q.5.17 Q.5.18 Q.5.19 Q.5.20 Q.5.21

Diquat dibromide Paraquat Strychnine Toxins of mycotoxin group Toxins of aflatoxin group

If the gastro-intestinal tract of a patient is infected with Vibrio cholera or Escherichia coli, is it sufficient to remove the pathogens from the system for the complete recovery of the patient? Explain. Ca and Na montmorillonites are more effective than palygorskite and sepiolite in the treatment for aflatoxin contamination. Why? Describe the applications of the clay minerals in the treatment of different types of enterotoxins. Compare the modern applications of clay minerals in the treatment of toxicity with their traditional applications. How diquatdibromide can be potentially harmful? What is paraquat? Why is it potentially harmful for human health? Give the chemical composition of the pesticides strychnine and trichothecene. What are their effects on human health? Give the chemical formula for T-2 Toxin. How is it produced in the cereal grains? How are the toxins of flatoxin group synthesized in the nuts and dried fruits by the microbes Aspergillus flavus and Aspergillus parasiticus? Write down the differences between exotoxins and endotoxins. How is enterotoxin synthesized by different species of Bacillus, Clostridium, Escherichia and Staphylococcus? How does the bacteria Vibriocholerae affect human health? What are the causes of hemorrhagic colitis and haemolytic uremia syndrome? How does smectite and kaolin adsorb the toxins of Vibrio cholerae and Escherichia coli?

Chapter 6 Q.6.1 Q.6.2 Q.6.3 Q.6.4

What do you think are the reasons for the extremely rapid spreading of the SARS-CoV-2? Why are a diverse group of viruses, including the SARS-CoV-2 viruses, named as coronaviruses? Explain with a diagram. Why is it very difficult to formulate an effective, generalised medication for COVID 19? Why are some mutant variants of the SARS-CoV-2 virus designated as the variants of concern?

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Q.6.5 Q.6.6 Q.6.7

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How does the SARS-CoV-2 virus enter the human body? Describe with schematic diagrams. What is the role of hACE2 (human angiotensin-converting enzyme 2) in the entry of SARS-CoV-2 virus inside the human body? Are the harmful effects of SARS-CoV-2 restricted to the human respiratory system only? Sketching a schematic diagram of the anatomy of human body, label the organs that can be affected by this virus. What are the transgenic animals? How do they help in pathogenic researches? What are the common modes of transmission of the SARS-CoV-2 virus? Which modes of transmission can be prevented by the following remedial measures? (a) (b) (c) (d) (e)

Use of hand gloves Maintaining sufficient distance from the infected individuals Application of surface sanitisers Use of proper face masks Washing hands with soap after touching some used medical appliance

Q.6.10 How do the alkali-based soaps and alcohol-based sanitisers destroy the SARS-CoV-2 virus? Q.6.11 Discuss the harmful effects of alkali-based soaps on human skin, and explain why the clay-based sanitisers are more suitable than the soaps for hand sanitisation. Q.6.12 Discuss the detrimental effects of alcohol-based hand rubs and sprays on human health, and explain the prospect of their substitution by clay-based formulations. Q.6.13 Describe the harmful effects of the conventional detergents on the environment. Which types of clay minerals will be suitable for the manufacture of clay-based detergents and why? Q.6.14 How can the clay minerals prevent the entry of SARS-CoV-2 virus into human body? The adsorptive property of clay minerals, described in Chaps. 1 and 2, is most important in their antiviral actions. Is there any other property of clay minerals that is important in their application against COVID-19? Q.6.15 Explain with schematic diagrams the application of clay-based disinfectants for hand sanitisation and disinfection of surfaces. Q.6.16 How are the organoclays synthesized? Why are they considered as better alternatives for production of clay-based hand sanitisers than pure clay or inorganic clay derivatives? Q.6.17 What are the advantages of amino clay hand gels over natural clay for hand sanitisation?

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Q.6.18 Among different types of clay minerals, those belonging to smectite and vermiculite groups were found to be most suitable for the production of surface disinfectants for the prevention of COVID-19. What do you think are the reasons for this? Q.6.19 If the COVID-19 patients are treated in a separate hospital situated in an isolated area, surrounded by sufficient open spaces and bare soil, is that expected to prevent transmission of the disease? Express your views in this regard. Q.6.20 Describe how the antimicrobial properties of clay minerals can be utilised to prevent the propagation of SARS-CoV-2 from biomedical wastes, and explain why this method of biomedical waste management is preferable over the other commonly used methods. Q.6.21 Clark et al. (1998) reported that a clay-based antimicrobial substance can efficiently adsorb the virus that causes certain types of diarrhoea of cattle. Is there any implication of this result in the treatment of COVID-19 of humans? Explain. Q.6.22 Which physical quantity is used for expressing quantitatively the binding capacity of a material? Give the definition of this physical quantity, and write down its dimension and SI unit. Q.6.23 Express your views on the feasibility of treatment of the SARS-CoV-2 infected patients with clay-based medicines. Q.6.24 Which properties of the clay minerals make them suitable for the production of drug delivery systems? Q.6.25 Explain the concept of repurposing of old drugs. What are the utilities of repurposed drugs in the treatment of COVID-19? Q.6.26 What are the roles of clay minerals in the treatment of COVID-19 with repurposed drugs? Q.6.27 What is an antibody? Why did some researchers postulate that nanoclaybased formulation scan be used as ‘pseudo antibodies’ against SARS-CoV2? Q.6.28 What is meant by synergistic action? Why some researchers expect that the nanoclay-based medicines may have dual actions against the SARS-CoV-2? Chapter 7 Q.7.1

Q.7.2

Q.7.3

The clay minerals can protect human health from a wide variety of microbes, including viruses and bacteria. Is there any difference in their actions against these two categories of microbes? Explain this elaborately, citing relevant sections of Chap. 2. What does the word ‘tailor-made’ mean? What is meant by a ‘tailor-made medicine’, and why is it believed that they can be produced from the clay minerals? How does the ability of a clay mineral to bind with other substances enhance its therapeutic attributes?

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Q.7.4

Q.7.5 Q.7.6 Q.7.7

Q.7.8 Q.7.9

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Discuss why the clays are preferable over many other medicine ingredients as the raw materials for the pharmaceutical industries in a developing nation, where large-scale productions of less expensive medicines are required. Discuss the suitability of clays as medicine ingredients from the point of view of the environmentalists. What is meant by ‘pharmacokinetic’ property? What is the important application of the nanomaterials having better pharmacokinetic properties? What are in vitro, in vivo and in silico studies of a medicine? Which of them do you think would be most reliable to establish the effectivity of a medicine? What are meant by in vitro and in vivo diagnostics? Which of them will help to obtain more reliable pathological report in less time? Which properties of nanoparticles make them suitable for the following medical applications? (a) Preparation of medicines (b) Pharmaceutical studies (c) Manufacture of surgical appliance

Q.7.10

Q.7.11 Q.7.12 Q.7.13 Q.7.14 Q.7.15

Q.7.16 Q.7.17 Q.7.18

You need to consult Sect. 7.2.2, and the relevant publications cited in Sect. 7.2. What is meant by ‘nanoclays’? explain whether the following statement qualifies as a definition of nanoclay: “Nanoclay is the very fine grained particles of any type of clay mineral”. What are the differences between clay nanocomposites and nanohybrids? explain with examples. Which property of the nanoclays make them suitable for the production of antiviral drugs? explain with example. What is meant by bioavailability of a medicine? Explain the role of nanoclays as the carrier of the anticancer drug curcumin. What are regenerative medicines? Describe the application of nanoclays in the production of such medicines. The application of nanoclay derivatives in food preservation and packaging industries have been described in Sect. 7.2.5. How is it relevant to the context of this book? express your views in this regard. What are Polymer–Clay Nanocomposites? why are they preferable over other materials in the food preservation and packaging? What are the two types of inhalable particulate matters? How do they affect the human health? What are the non-clay components of the inhalable particulate matters?

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Q.7.19 The airborne fine particles of clay minerals are major components of inhalable particulate matters. If all the clay mines and clay-based industries are stopped, will that help to remove all the clay particles from the air? Explain your answer with reasons. Q.7.20 In addition to air pollution, what are the other potential environmental hazards of the clay-based industries? Q.7.21 In many countries throughout the world, some factories have been relocated or even abolished for their detrimental effects on the environment. Is it required for the factories of clay-based medicines also? Express your views in this regard. Q.7.22 Which properties of clay minerals are required to be studied systematically and more elaborately for the production of more effective medicines? Explain with reasons. Q.7.23 Are the in vitro studies carried out at neutral pH sufficient for finding out the effectivity of a clay mineral against a particular microbe or toxin? Explain. Q.7.24 Which research methodology would you suggest that may help to identify the most suitable clay mineral for the production of a particular type of antimicrobial or antitoxic medicine? Q.7.25 Point out the lacunae in our understanding regarding the virus adsorption mechanism of the clay minerals. What would you recommend to improve the present state of knowledge on this subject? Q.7.26 Suggest the areas for future researches that may help to understand the bactericidal reactions of the clay minerals, and facilitate the production of more effective antibacterial drugs. Q.7.27 How do you think the researches on clay nanocomposites and nanohybrids may enrich the modern pharmaceutical industries? Q.7.28 Study the chart given in Fig. Q.7.28, and mention which of the applications of clays, nanoclays, and their derivatives given therein fall within the purview of this book. Also indicate the numbers of chapters, sections or subsections in which these applications of clays or their derivatives have been explained.

Think for a While

159

Fig. Q.7.28 Chart showing some important attributes of clays, nanoclays,and their derivatives, and the applications of these attributes in various fields

References Carretero, M.I. (2002). Clay minerals and their beneficial effects upon human health: A review. Applied Clay Science, 21: 155–163. Carlson, G.F., Woodard, F.E., Jr., Wentworth, D.F. and 0.J. Sproul (1968). Virus min activation on clay particles in natural waters. J. Water Pollut. Contr. Fed., 40: R98–R106. Clark, K.J., Sarr, A. B., Grant, P. G., Phillips, T. D. and G. N. Woode (1998). In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus. Veterinary Microbiology 63, 137–146. Cunningham, T.B., Koehl, J.L., Summers, J.S. and S. Haydel (2010). Dependent metal ion toxicity influences of the antibacterial activity of two naturals mineral mixtures. PLoS One,5(3): e9456.

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Lipson, S.M. and G. Stotzky (1983). Adsorption of reovirus to clay minerals: Effects of cation-exchange capacity, cation saturation, and surface area. Applied and Environmental Microbiology, 46(3): 673–682. Schaub, S.A. and B.P. Saglk (1975). Association of enteroviruses with natural and artificially introduced colloidal solids in water and infectivity of solids–associated virions. Appl.Microbiol., 30: 212–222. Williams, L.B., Haydel, S.E., Giese, R.F. and D . D . Eberl (2008). Chemical and mineralogical characteristics of french green clays used for healing. Clays and Clay Minerals,56(4): 437–452.

Index of Pathogens

A Acinetobacter baumannii, 65 Acinetobacter calcoaceticus, 65 Alpha (B.1.1.7) variant of SARS-CoV-2, 94 A. Parasiticus, 83 Aspergillus flavus, 83

Fusarium poae, 83 Fusarium sporotrichioides, 83

B Bacillus, 84 Bacteroidesfragilis, 85 Beta (B.1.351) variant of SARS-CoV-2, 94 Bovine Coronavirus (BCoV), 110, 111

H Helicobacter pylori, 68, 73

C Clostridium, 84, 85 Clostridium difficile, 85 Clostridium perfringens, 84

D Delta (B.1.617.2) variant of SARS-CoV-2, 94

E E. coli, 35, 42, 84, 86 Encephalomyocarditis, 28 Escherichia coli, 35, 36, 41, 63, 84,

F F. equiseti, 83 F. poae, 83 F. sporotrichioides, 83 Fusarium graminearum, 83

G Gamma (P.1) variant of SARS-CoV-2, 94

L Legionella pneumophila, 65 M Mengovirus, 28 MERS-CoV, 92 Mycobacterium marinum, 35 Mycobacterium smegmatis, 35 Mycobacterium ulcerans, 42, 57, 63 O Omicron (B.1.1.529) variant of SARS-CoV-2, 94 P Pathogenic bacteria, 57, 62 Poliovirus, 26 Pseudomonas aeruginosa, 35, 63 R Reovirus, 26, 29, 30, 32, 33 Rotavirus, 26, 110

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162 S Salmonella aureus, 35 Salmonella enteric, 35, 63 SARS-CoV, 92–95 SARS-CoV-2, 91–97 Serovar typhimurium, 35, 63 Staphylococcus, 84

Index of Pathogens Staphcylococcus aureus, 35, 63, 65 Staphylococcus epidermidis, 36

V Vibrio, Vibrio cholerae, 84

Subject Index

A ABHS, health effects, 102, 103 Acne, 68 Adsorbates, 20 Adsorbents, 20 Adsorption, 20, 21, 26–33, 44 Adsorption coefficient, 80 Adsorption, controlling factors, 20 Adsorption, definition, 20 Adsorption isotherm, 80, 81 Adsorption mechanism, 27, 29, 31, 45 Adsorption of bacteria, see Bacteria adsorption Adsorption of virus, see Virus adsorption Adsorption, organic cation, 45–47 Adsorption, organic molecules, 21 Adsorption, organic toxins, 81 Aflatoxin group, 83 Alcohol-Based Hand Sanitisers, see ABHS Alcohol-Based Hand Sanitisers (ABHS), 102, 105, 108 Aliettite, 5 Alimentary allergy, 68, 69 Alimentary toxic aleukia, 83 Alkali-based soaps, 61 Allochromatic, 16 Allophane, 130 Allophone, 3 Amesite, 4 Aminoclays, 107 Anaphylaxia, 69 Angiotensin-Converting Enzyme 2 (ACE2), ACE2 proteins, 34, 95 Antibacterial action, 57 Antibacterial effectiveness, 66 Antibacterial mechanism, 66 Antibacterial treatment, 64

Antibiotic properties, 56 Antibiotic therapy, 57 Antibody, 41, 111 Antifungal treatment, 64 Antigens, 41, 111 Antimicrobial, 55, 61 Antimicrobial actions, 61 Antimicrobial agent, 63 Antimicrobial applications, 62 Antimicrobial cations, 43, 61 Antimicrobial effect, 63 Antitoxic actions, 62 Antitoxic actions, controlling factors, 43 Antitoxic actions, mechanism, 43 Antitoxic properties, 61 Antitoxic reactions, 55 Antitoxin applications, 62 Aripiprazole, 65, 71 Associated minerals, 1–3 Associated phases, 1, 3

B Bacteria adsorption, 34, 39, 40 Bacteria adsorption, effects of ionic concentrations, 41 Bacteria adsorption, effects of pH, 41 Bacteria adsorption, electrical double layer forces, 40 Bacteria adsorption, electrostatic attraction, 39 Bacteria adsorption, hydrophobic attraction, 40 Bacteria adsorption, Lewis acid-base interaction, 40 Bacteria adsorption, Van der Waals forces, 40

© Capital Publishing Company, New Delhi, India 2023 B. Ghosh and D. Chakraborty, Clay Minerals, https://doi.org/10.1007/978-3-031-22327-3

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164 Bactericidal actions, 34, 42, 61 Bactericidal process, role of Fe2+ , 38 Bactericidal process, role of pyrite, 39 Bacteriostatic actions, 34 Beidellite, 5 Bentonite, 6, 82, 83, 108 Berthierine, 4 Bioavailability of medicines, 132 Boehmite, 2 Brammallite, 5 Breast cancer, 74 Bridging O2 –, 6, 8 Brindleyite, 4 Brinrobertsite, 5 Buffer, 38 Buffer, hydrogen ion, 38 Buffer, metal-ion, 38 Buffer, redox, 38 Buruli ulcer, 42, 57, 63

C Ca-smectite, 35 Cation exchange, 17 Cation Exchange Capacity (CEC), 16, 18, 19 Cation Exchange Capacity, see (CEC) Cation exchange reaction, 65 Cation substitution, 16 Cation, virus bridge, 27, 32 CEC, clay minerals, 19 CEC, definition, 18 CEC, role in virus adsorption, 28–31 CEC, Role in toxin adsorption Centimole, 18 Chain silicate, 13 Chemotherapeutic drug, 71 Chemotherapy medication, 74 Chromophores, 16 Clay based hand gel, 107 Clay-based hand sanitisers, 105 Clay-based medicines, 55 Clay based medicines, advantages, 124–127 Clay based medicines, economic consideration, 125 Clay based medicines, environmental considerations, 125 Clay based medicines, health considerations, 125 Clay based medicines, therapeutic considerations, 128 Clay-based surface disinfectants, 108 Clay-cation-bacteria bridge, 40

Subject Index Clay, constituents of, 1–3 Clay, definition, 1 Clay-drug nanohybrid, 65, 131 Clay, dual actions against COVID-19, 115 Clay, environmental hazards, 135 Clay, future researches, 137–141 Clay, health hazards, 136 Clay, impacts on water resources, 136 Clay leachate, 35, 36, 38 Clay mineral, definition, 1 Clay minerals, 55, 56, 61, 62 Clay minerals, antibacterial actions, 34, 35 Clay minerals, CEC, 19 Clay minerals, colour, 15, 16 Clay minerals, expandable, 35 Clay minerals, general chemical composition, 3 Clay minerals, internal structures, 6 Clay nanocomposites, 127, 130, 131, 133, 134 Clay nanohybrids, 115 Clay nanoparticles, 65 Clay nanotubes, 132 Clays-alone medicines, 111 Clays, antibacterial, 35, 37, 41 Clays, antitoxic actions, 43 Clays, non-antibacterial, 35, 36 Clay, treatment of bovine coronavirus, 110, 111 Clay, treatment of rotavirus, 110 Coagulates, 26 Cohesive Energy Density (CED), 105 Colitis, 67 Colonic fermentation, 68, 71 Colonic transit, 68 Concentration gradient, 62 Connective tissue, 72 Coronam, 92 Coronaviridae, 92, 110 Coronavirus disease, 91 Coronaviruses, 92, 110 Corrensite, 5 Corundum, 2 Counterion, 28 Counter ions, 44 COVID-19, 91 COVID-19, dual actions of clay, see Clay, dual actions against COVID-19 COVID-19, prevention, 98, 105 COVID-19, synergistic actions of clay, see Clay, Dual actions against COVID-19 COVID-19, treatment, 109–111

Subject Index Cronstedtite, 4

D DDS, see Drug Delivery System Deoxyribonucleic Acid (DNA), 92, 114 Dermatological pathologies, 58 Detergent, 103, 104, 108 Detergent, amphoteric, 103 Detergent, anionic, 103, 104 Detergent, cationic, 103, 104 Detergent, environmental effects, 104 Detergent, health effects, 104 Detergent, non-ionic, 103, 104 Detoxifying agents, 71, 79 Diacetylrhein, 65 Diadochy, 16 Diarrhoea, 64 Diaspore, 2 Dickite, 4 Diffuse layer, 44, 45 Diffusion coefficient, 62 Digestive tract, 62, 63 Di-octahedral phyllosilicates, 8 Diosmectite treatment, 82 Diquat dibromide, 82 Disinfectants, 16 Distribution coefficient, 62 Double-stranded nucleic acid, 92 Drug Delivery System (DDS), 113, 114 Drug molecules, 62 Duodenal ulcer, 72 Duodenum, 72

E Edible clay, 58 Electric double layer, 44 Electrolytes, 26 Electrophoretic mobility, 32 Endotoxins, 83 Enterotoxin, 84, 85 Environmental hazards of clay, see Clay, Environmental hazards Epithelial cells, 68 Epithelial surface, 67, 72 Equation, 80 Equivalent weight (Eq), 18 Esophageal ulcer, 72 Eutrophication, 104 Excipient, 67, 74 Exotoxins, 84

165 F Falcondoite, 5 Fangotherapy, 64, 72 Fatty tissues, 72 Fenton reaction, 37, 39 Fe-smectite, 35 Flocculation, 27, 28 Flocculation power, 28 Flocs, 26, 28 Fraipontite, 4 French clay, 57 Fuller’s earth, 82, 83 Fungal infections, 64 G Gastric tissues, 56 Gastric ulcer, 72 Gastritis, 68 Gastroduodenal ulcers, 72 Gastrointestinal ailments, 72 Gastrointestinal disorders, 72 Gastrointestinal (GI) tract disorder, 63 Gastrointestinal glycoproteins, 67 Gastrointestinal mucosa, 82 Gastrointestinal mucus, 67 Gastrointestinal tract, 56 Geophagy, 55, 66 Gibbside, 2 Glauconite, 5 Glycopeptides, 64 Glycoprotein, 92, 95, 110 Glycoprotein polymers, 67 Goethite, 2 Gouy–Chapman model, 44 Gouy layer, 44, 45 Gram-negative bacteria, 84 Green clay, 57 H Haber, Weiss reaction, 37 Haemolytic uraemia, 84, 86 Halloysite, 4 Halloysite (Hydrated), CEC, 19 Halloysite, in DDS, 113 Halloysite nanotubes, 132 Healing clay, 58 Health hazards of clay, see Clay, Health hazards Heat labile, 84 Heavy metal, 62 Hectorite, 5, 114 Helmholtz model, 44

166 Hematite, 2 Hemorrhagic colitis, 84, 85 Herbicides, 82 Heteroionic clay minerals, 29 Homoionic clay minerals, 29 Human Angiotensin-Converting Enzyme 2 (hACE2), 105, 111, 115 Hydrated sodium calcium aluminosilicate clay (HSCAS), 110 Hydrobiotite, 5 Hydrophobic interaction, 34, 41 Hydroxide, 2 Hydroxyl groups, 8

I Idiochromatic, 15, 16 Illite, 3, 6 Illite, CEC, 19 Illite, composition, 5 Illite, structure, 12 Immune system, 95, 97, 111 Immunocompetence, 41 Immunoglobulin, 41 Immunosuppressant, 42 Imogolite, 3 Indomethacin, 72 Infectious diseases, 56 Interlayer cations, 9 Interlayer spaces, 9, 29, 35, 43 Ionic substitution, 16

K Kaolinite, 3, 4, 68, 69, 108 Kaolinite, CEC, 19 Kaolinite clay, 64 Kaolinite, composition, 4 Kaolinite, in DDS, 113 Kaolinites, structure, 11 Kellyite, 4 Kulkeite, 5

L Laponite, 114, 115 Lepidocrocite, 2 Linear, 80, 81 Lipid-polysaccharide complexes, 83 Lipid solvents, 93, 110 Lipopolysaccharides, 83 Lizardite, 4 Loughlinite, 5

Subject Index M Magnetite, 2 Mast cells, 68, 72 Methicillin, 64 Microbes, 55, 56, 62 Microorganisms, 26, 39, 68 Milli Equivalent (mEq), 18 Mineral classes, 3 Mineral groups, 3 Mineral species, 3 Mineromedicinal water, 62, 74 Mixed layer clays, 3 Mixed layer clays, composition, 5 Montmorillonite, 5, 57, 65, 68, 130, 131, 133, 134, 136 Montmorillonite, in DDS, 113 Montmorillonite, in PCN, 134 Morphological distortions, 34 Mucosa, 62, 67 Mucus, 73 Mucus gel, 67 Mud therapy, 64, 73 Mycobacterial diseases, 57 Mycolactone toxin, 42, 57 Mycotoxin group, 83 N Nacrite, 4 Na-kaolinite, 33 Na-montmorillonite, 33 Nanoclay, 105, 130–134, 141 Nanoclay, anticancer medicine, 132 Nanoclay derivatives, 131 Nanoclay derivatives, in food packaging, 133 Nanoclay derivatives, in food preservation, 133 Nanoclay, drug delivery system, 131 Nanoclay, dual antimicrobial actions, 132 Nanoclay, in food preservation and packaging, 133, 134 Nanoclay, medicine ingredients, 131 Nanoclay, regenerative medicines, 133 Nanoclay, taste masking of drugs, 133 Nanocomposites, 79, 80, 130–134 Nanohybrids, 65, 130, 131, 133 Nanomaterials, 127–133 Nanomaterials, drug carriers, 128 Nanomaterials, in vitro diagnostics, 128 Nanomaterials, in vivo diagnostics, 128 Nanomaterials, properties, 129 Nanomaterials, surgical instruments, 128 Nanomedicines, 128

Subject Index Nanoparticles, 125, 127–130 Nanoscale, 127, 128, 131, 134 Nanotechnology, 125 Nanotechnology, in medical sciences, 128, 129, 133 Natural clays, 56, 62 Nepouite, 4 Niclosamide (NIC), in COVID-19 treatment, see Repurposed Niclosamide Nidovirales, 92, 110 Non-bridging oxygen, 6 Nonlinear adsorption isotherm, 81 Nonsteroidal anti-inflammatory drugs, 73 Nontronite, 5 Non-ulcer dyspepsia, 73 O Octahedral, 8 Oesophagus, 72 O-layer, 8 Opuntiahumifusa plant, 107 Organic moieties, 107 Organoclay, 106, 107 Organophilic surfaces, 107 Orthocoronavirinae, 92 Osteoarthritis, 65 Oxide, 2 P Palygorskite, 69 Palygorskite, composition, 5 Palygorskite, sepiolite, 3 Palygorskite–sepiolite, adsorption, 21 Palygorskite, sepiolite, CEC, 19 Palygorskite, sepiolite, structure, 13 Paraquat, 82 Particulate Matters (PM), 135 Pathogens, 55, 58 PCN production: In situ polymerization, 131 PCN production: melt processing, 131 PCN production: solution method, 130 Pear diseases, 64, 73 Peloidtherapy, 58 Pelotherapy, 57 Peplomer protein, 92 Peptic ulcer, 72, 73 Pesticides, 82 Pharmaceutical applications, 62 Pharmaceutical formulations, 63 Pharmaceutical industries, 61

167 PH buffer, 38 Phyllosilicate subclass, 3, 6 Phyllosilicates, t-o structure, see t-o layer Phyllosilicates, t-o-t structure, see t-o-t layer Phyllosilicates, t-o-t-c structure, seet-o-t-c layer Phytotoxin, 82 PM2.5 , 135 PM10 , 135 Polymer-Clay Nanocomposites, see PCN Polymer-Clay Nanocomposites (PCN), 130, 131, 134 Pseudo-antibodies, 111 Pyloric sphincter, 73 R Rectorite, 5 Redox potential, 38, 39 Regenerative medicines, 128, 133 Repurposed Niclosamide, 113 Repurposed Rifampicin, 114 Repurposing of drugs, 113 Rheological properties, 61 Rifampicin (Rif), in COVID-19 treatment, see Repurposed Rifampicin Ribonucleic Acid (RNA), 92, 94, 114 S Salicylic acid, 73 Saponite, 5 SARS-CoV-2, effects on human health, 97, 98 SARS-CoV-2, entry in human cell, 95 SARS-CoV-2, transmission, 98, 102, 105, 108, 109 Sauconite, 5 Schulze-hardy rule, 28, 30 Sepiolite, 69 Sepiolite, composition, 5 Silicate class, 3, 6 Single-stranded nucleic acid, 92 Skin disease, 64 Small intestine, 73 Smectite, 3, 57, 63, 69 Smectite, CEC, 19 Smectite group, 82, 83, 108 Smectites, composition, 5 Smectite,Trioctahedral, see Hectorite Smectite, structure, 12 Sorption coefficient, 80–82 Specific surface area, 13

168 Specific surface area, calculation, 13, 14 Spike protein, 95, 96, 105, 111, 115 Spike protein, binding affinity, 95 Spike protein, subunit S1, 93, 95, 96 Spike protein, subunit S2, 93, 95 Spikes of virus, see virus, spikes Stern layer, 44, 45 Stern model, 32, 48 Stevensite, 5 Stomach cancer, 74 Strychnine, 82 Sublethal impact, 74 Surface charge density, 31, 32 Surface sprays, 102, 103 Surfactant, 103, 104, 106 Suspended Particulate Matter (SPM), 135 Swinefordite, 5 Synergistic actions, 74 Synergistic effect, 63

T T-2 toxin, 83 Talc, 70 Tetrahedral layer, 6 Tetrahedron,[SiO4 ]4 , 6 Thalassotherapy, 58 Therapeutic applications, 62 Thermal mud, 65 T-Layer, see Tetrahedral Layer Toilet soaps, health effects, 100 T-o layer, 8, 12 Topical applications, 61 Topical medication, 75 Tosudite, 5 Total surface charge, 45 T-o-t-c layer, 9, 12, 17 T-o-t layer, 8, 9, 12, 14, 17, 20 Toxin-induced erosions, 82 Toxins, 58, 61 Traditional medicines, 55 Transdermal drug delivery, 74 Transdermal drug delivery system, 62 Transdermal route, 65, 74 Transgenic animals, 98 Transition elements, 43

Subject Index Trastuzumab, 74 Trichothecene, 83 Tri-octahedral, 8

U Ulcers, 57

V Variants of Concern (VOC), 94 Vermiculite, 3 Vermiculite, CEC, 19 Vermiculite group, 108 Vermiculites, composition, 5 Vermiculite, structure, 12 Verotoxin of EHEC, 84 Virus adsorption, 27, 28, 31, 32 Virus adsorption, effects of CEC, 29 Virus adsorption, effects of specific surface, 31 Virus adsorption, effects of surface charge density, 31 Virus adsorption, effects of Van der Waals forces, 28 Virus adsorption, hydrogen bonding, 28 Virus, clay bond, 33 Virus, envelope, 92 Viruses, 61, 68 Virus, lipid membranes, 92 Virus, peplos, 92 Virus, spikes, 92 Volkonskoite, 5

W Wonder drugs, 56 Wonesite, 5

Y Yofortierite, 5

Z Zeta potential, 32