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Biointeractions of
Nanomaterials
Edited by
Vijaykumar B. Sutariya
Yashwant Pathak
Biointeractions of
Nanomaterials
Biointeractions of
Nanomaterials
Edited by
Vijaykumar B. Sutariya
University of South Florida
College of Pharmacy
Tampa, Florida, USA

Yashwant Pathak
University of South Florida
College of Pharmacy
Tampa, Florida, USA

Boca Raton London New York

CRC Press is an imprint of the

Taylor & Francis Group, an informa business
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742

© 2015 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

Version Date: 20140425

International Standard Book Number-13: 978-1-4665-8239-2 (eBook - PDF)

This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been
made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or
liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed
in this book by individual editors, authors or contributors are personal to them and do not necessarily reflect the views/opinions
of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care
professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of
the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the
rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently veri-
fied. The reader is strongly urge to consult the relevant national drug formulary and the drug companies’ printed instructions,
and their websites, before administering any of the drugs recommended in this book. This book does not indicate whether a
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 Dedicated to the loving memory of my father, Bhadabhai
Chakubhai Sutariya, who passed away on April 22, 2013. He was my
role model and mentor throughout my life and whatever I have
achieved in life is because of his blessings. I would also like to
dedicate this book to the memory of Swami Vivekananda; the
world celebrated the 150th birthday of Swamijee in 2013.

Vijaykumar B. Sutariya

To the loving memories of my parents and Dr. Keshav Baliram Hedgewar,

who showed the right direction; my wife Seema, who gave my life positive
meaning; and my son Sarvadaman who gave a golden lining to my life.

Yashwant Pathak
Contents
Foreword............................................................................................................................................ix
Preface...............................................................................................................................................xi
Editors............................................................................................................................................. xiii
Contributors...................................................................................................................................... xv

Chapter 1 Introduction—Biointeractions of Nanomaterials: Challenges and Solutions...............1

Vijaykumar B. Sutariya, Vrinda Pathak, Ana Groshev, Mahavir B. Chougule,
Sachin Naik, Deepa Patel, and Yashwant Pathak

Chapter 2 Nanoparticle Exposures in Occupational Environments............................................ 49

Li-Hao Young, Ying-Fang Wang, Ching-Hwa Chen, Chun-Wan Chen,
and Perng-Jy Tsai

Chapter 3 Physicochemical Characterization–Dependent Toxicity of Nanoparticles................. 73

Jigar N. Shah, Ankur P. Shah, Hiral J. Shah, and Vijaykumar B. Sutariya

Chapter 4 Cytotoxicity of Stimuli-Responsive Nanomaterials: Predicting Clinical

Viability through Robust Biocompatibility Profiles.................................................. 103
Daniel Wehrung and Moses O. Oyewumi

Chapter 5 Biosensing Devices for Toxicity Assessment of Nanomaterials............................... 117

Evangelia Hondroulis, Pratik Shah, Xuena Zhu, and Chen-Zhong Li

Chapter 6 Carbon Nanotubes and Pulmonary Toxicity............................................................. 131

Malay K. Das and Charles Preuss

Chapter 7 Nanotoxicity of Polymeric and Solid Lipid Nanoparticles....................................... 141

Dev Prasad and Harsh Chauhan

Chapter 8 Analytical Characterization of Nanomaterials in Biological Matrices

for Hazard Assessment.............................................................................................. 159
Mingsheng Xu, Daisuke Fujita, Huanxing Su, Hongzheng Chen,
and Nobutaka Hanagata

Chapter 9 Nanoparticles and Human Health: A Review of Epidemiological Studies............... 175

Vijaykumar B. Sutariya, Ana Groshev, Vivek Dave, Hardeep Saluja,
Deepak Bhatia, Prabodh Sadana, and Yashwant Pathak

vii
viii Contents

Chapter 10 Toxicogenomic Approaches to Understanding the Toxicity of Nanoparticles..........209

Qiwen Shi, Mahavir B. Chougule, Vijaykumar B. Sutariya, and Deepak Bhatia

Chapter 11 Nanomaterial-Based Gene and Drug Delivery: Pulmonary Toxicity

Considerations........................................................................................................... 225
Mahavir B. Chougule, Rakesh K. Tekade, Peter R. Hoffmann, Deepak Bhatia,
Vijaykumar B. Sutariya, and Yashwant Pathak

Chapter 12 Cardiovascular Toxicity of Nanomaterials................................................................249

Saijie Zhu and Minghuang Hong

Chapter 13 Toxicity of Nanomaterials on the Gastrointestinal Tract.......................................... 259

Jayvadan Patel and Vibha Champavat

Chapter 14 Toxicity of Nanomaterials on the Liver, Kidney, and Spleen................................... 285

Jayvadan Patel and Anita Patel

Chapter 15 Regulatory Implications of Nanotechnology............................................................ 315

Lynn L. Bergeson and Michael F. Cole

Chapter 16 Ocular Toxicity of Nanoparticles.............................................................................. 347

Aditya Grover, Anjali Hirani, Yong Woo Lee, Vijaykumar B. Sutariya,
and Yashwant Pathak

Chapter 17 Genotoxicity of Nanoparticles.................................................................................. 353

Amaya Azqueta, Leire Arbillaga, and Adela López de Cerain

Chapter 18 Interactions of Polysaccharide-Coated Nanoparticles with Proteins........................ 365

Christine Vauthier

Chapter 19 Models for Risk Assessments of Nanoparticles........................................................ 383

Sanjay Dey, Bhaskar Mazumder, and Yaswant Pathak

Chapter 20 Immunotoxicity of Carbon Nanoparticles................................................................. 425

Paulami Pal, Bhaskar Mazumder, and Yaswant Pathak
Foreword
Nanomaterials are those in the nanometer range (10−9 m). These
incredibly small particles can be organic or inorganic, with examples
ranging from poly(lactic-co-glycolic acid) or gold nanoparticles to
carbon nanotubes and quantum dots. These particles may be used to
encapsulate drugs, recognize biological markers, or visualize body
tissues among many other possibilities, all enabling their widespread
application in biology, medicine, and pharmaceutics. Indeed, these
nanomaterials may have beneficial effects that have not even been
imagined.
The small size of these particles provides an enormous surface
area, which is ideal for interactions with cells on a molecular level,
but also raises the question of their biosafety. The chemical composi-
tion of the diverse nanomaterials available for biological interactions
may have unforeseen consequences in living systems. Whether the good that these interactions
accomplish outweighs the risk of harm will have to be addressed before nanomaterials are used on
a wide scale, especially in biological systems.
This book is a collaborative effort of the editors Drs. Vijaykumar B. Sutariya and Yashwant
Pathak and the numerous contributors who are leading scientists in this field. The subject mat-
ter is of prime importance in the area of nanotechnology and its applications. These contributors,
knowledgeable and experienced in their field, attempt to elucidate the potential biointeractions of
nanomaterials with their respective applications in efforts to answer the questions posed above. This
book presents the possible biointeractions of various nanomaterials with a number of different body
tissues in a multitude of applications. I would like to congratulate Drs. Vijaykumar B. Sutariya and
Yashwant Pathak at the University of South Florida for editing this important and timely book.
It is my great pleasure to write a foreword and present to you Biointeractions of Nanomaterials.
I sincerely hope you will gain as much insight as I did from these chapters.

Shyam S. Mohapatra, PhD, MBA, FAAAAI, FNAI

Distinguished USF Health Professor and Director
Division of Translational Medicine-USF Nanomedicine Research Center
Vice Chair of Research
Department of Internal Medicine
President, USF Chapter of the National Academy of Inventors

ix
Preface
The purpose of this book is to focus on the biointeractions of nanomaterials, an area that has not
been previously addressed in detail. It also covers various techniques and tests that have been devel-
oped to evaluate the toxicity of materials at the nanolevel. The interactions of nanomaterials and
nanosystems within biosystems are a concern for the scientific community.
This book is targeted toward academic researchers as well as industry members who are involved
in the development of nanosystems. Many graduate schools have initiated courses in nanotechnol-
ogy and applications, and this book will be a great resource for students as well as professors.
Additionally, this will be a useful tool for industrial scientists investigating technology to update
their nanotoxicology and nanosafety understanding.
The objective of the book is to address issues related to the toxicity and safety of nanomaterials
and nanosystems. It also covers the interactions of these in biological systems, and various tools and
methods used to evaluate toxicity and safety issues.
The volume comprises 20 chapters written by leading scientists in the field of nanotechnol-
ogy. Chapter 1 covers the challenges and solutions of biointeractions of nanomaterials. This is fol-
lowed by three chapters that address the assessment and characterization of nanosystems in the
bioenvironment.
The next group of chapters covers toxicity and includes biosensing devices for toxicity assess-
ment, carbon nanotubes, and pulmonary toxicity, as well as nanotoxicity of solid lipid nanoparticles.
The final group of chapters from 8 to 20 covers nanosafety concerns and solutions. Each of these
chapters delves into the effects of nanoparticles on different organs and sheds light on regulatory
implications of nanomaterials.
We sincerely hope this book gets an overwhelming response from the scientific community in
the field of nanotechnology.
We thank and acknowledge our families, the publishers, and our contributing authors. We would
also like to acknowledge Aditya Grover, Anastasia Groshev, and Anjali Hirani for their assistance
in editing and obtaining copyright clearance as well as the staff of Taylor & Francis who assisted in
shaping this wonderful book in the field of nanotechnology.

Vijaykumar B. Sutariya
Yashwant Pathak

xi
Editors
Dr. Vijaykumar B. Sutariya earned his bachelor of pharmacy and master of pharmacy from
L. M. College of Pharmacy, Gujarat University, Ahmedabad, India and his PhD in pharmacy from
The M.S. University of Baroda, Vadodara, India. He did his postdoctoral training in the field of
pharmaceutics and drug delivery at Butler University, Indianapolis, Indiana.
Dr. Sutariya is an assistant professor in the Department of Pharmaceutical Sciences at the
University of South Florida (USF) College of Pharmacy. He has a joint appointment with the
Department of Internal Medicine, Division of Translational Medicine at USF.
Dr. Sutariya has published more than 30 research papers in peer-reviewed journals and has pre-
sented at various national and international meetings. He is a reviewer of many international journals
and an editorial board member of more than six journals related to drug delivery and pharmaceutical
sciences. Dr. Sutariya’s research is focused on the development of novel drug delivery systems such
as nanoparticles, liposome, and thermoreversible gel. His main research focus is on brain-targeted
drug delivery and ocular drug delivery. Dr. Sutariya is currently serving as a coinvestigator on two
NIH grants (R01 and R15). In addition to research, Dr. Sutariya teaches various courses related to
pharmaceutics in the Doctor of Pharmacy curriculum.

Dr. Yashwant Pathak completed his MS and PhD in pharmaceutical technology at Nagpur
University, India and his EMBA and MS in conflict management from Sullivan University,
Kentucky. He is an associate dean for faculty affairs at the College of Pharmacy, University of
South Florida, Tampa, Florida. With extensive experience in academia as well as industry, he has to
his credit more than 100 publications, 5 books on nanotechnology, 4 books on nutraceuticals, and
several books on cultural studies, including 2 on aging studies from an Indian perspective. His areas
of research include drug delivery systems and their characterization in animal models.

xiii
Contributors
Leire Arbillaga Mahavir B. Chougule
Department of Pharmacology and Toxicology Department of Pharmaceutical Sciences
University of Navarra University of Hawaii
Pamplona, Spain Hilo, Hawaii

Amaya Azqueta Michael F. Cole

Department of Pharmacology and Toxicology Bergeson & Campbell, P.C.
University of Navarra Washington, D.C.
Pamplona, Spain
Malay K. Das
Lynn L. Bergeson College of Pharmacy
Bergeson & Campbell, P.C. University of South Florida
Washington, D.C. Tampa, Florida

Deepak Bhatia Vivek Dave

Department of Pharmaceutical Sciences Wegmans School of Pharmacy
Northeast Ohio Medical University St. John Fisher College
Rootstown, Ohio Rochester, New York

Vibha Champavat Adela López de Cerain

Nootan Pharmacy College Department of Pharmacology and Toxicology
North Gujarat, India University of Navarra
Pamplona, Spain
Harsh Chauhan
Department of Pharmacy Sciences Sanjay Dey
Creighton University Department of Pharmaceutical Sciences
Omaha, Nebraska Dibrugarh University
Dibrugarh, India
Ching-Hwa Chen
Department of Environmental and
Daisuke Fujita
Occupational Health, Medical College
Advanced Key Technologies Division
National Cheng Kung University
National Institute for Materials Science
Tainan, Taiwan
Ibaraki, Japan
Chun-Wan Chen
Institute of Occupational Safety and Health Ana Groshev
Ministry of Labor College of Pharmacy
Taipei, Taiwan University of South Florida
Tampa, Florida
Hongzheng Chen
Department of Polymer Science and Aditya Grover
Engineering College of Pharmacy
Zhejiang University University of South Florida
Zhejiang, China Tampa, Florida

xv
xvi Contributors

Nobutaka Hanagata Moses O. Oyewumi

Interdisciplinary Laboratory for Nanoscale Department of Pharmaceutical Sciences
Science and Technology Northeast Ohio Medical University
National Institute for Materials Science Rootstown, Ohio
Ibaraki, Japan
Paulami Pal
Anjali Hirani Department of Pharmaceutical
School of Biomedical Engineering and Sciences
Sciences Dibrugarh University
Virginia Tech Dibrugarh, India
Blacksburg, Virginia
and Anita Patel
College of Pharmacy Nootan Pharmacy College
University of South Florida North Gujarat, India
Tampa, Florida
Deepa Patel
Peter R. Hoffmann Parul Institute of Pharmacy and Research
Department of Cell and Molecular Biology Gujarat, India
John A. Burns School of Medicine
Honolulu, Hawaii Jayvadan Patel
Nootan Pharmacy College
Evangelia Hondroulis North Gujarat, India
College of Engineering and Computing
Florida International University Vrinda Pathak
Miami, Florida College of Pharmacy
University of South Florida
Minghuang Hong Tampa, Florida
Pharmaceutical Crystal Engineering Research
Group
Yashwant Pathak
Shanghai Institute of Pharmaceutical Industry
College of Pharmacy
Shanghai, China
University of South Florida
Tampa, Florida
Yong Woo Lee
School of Biomedical Engineering and Sciences
Virginia Tech Dev Prasad
Blacksburg, Virginia School of Pharmacy
Massachusetts College of Pharmacy and
Chen-Zhong Li Health Sciences
College of Engineering and Computing Boston, Massachusetts
Florida International University
Miami, Florida Charles Preuss
Department of Molecular Pharmacology and
Bhaskar Mazumder Physiology
Department of Pharmaceutical Sciences Morsani College of Medicine
Dibrugarh University University of South Florida
Dibrugarh, India Tampa, Florida

Sachin Naik Prabodh Sadana

Formulation Department Department of Pharmaceutical Sciences
SunPharma Advanced Research Co. Ltd. Northeast Ohio Medical University
Gujarat, India Rootstown, Ohio
Contributors xvii

Hardeep Saluja Rakesh K. Tekade

College of Pharmacy Department of Pharmaceutical Sciences
Southwestern Oklahoma State University University of Hawaii at Hilo
Weatherford, Oklahoma Hilo, Hawaii

Perng-Jy Tsai
Ankur P. Shah
Department of Environmental and
Pharmaceutical Technology Center
Occupational Health
Zydus Cadila Healthcare Ltd.
National Cheng Kung University
Gujarat, India
Tainan, Taiwan

Hiral J. Shah Christine Vauthier

Department of Pharmaceutics Institut Galien Paris-Sud
Arihant School of Pharmacy and BRI Université de Paris Sud Faculté de Pharmacie
Gujarat, India Chatenay-Malabry, France

Jigar N. Shah Ying-Fang Wang

Department of Pharmaceutics Department of Environmental and
Nirma University Occupational Health
Ahmedabad, India Medical College
National Cheng Kung University
Tainan, Taiwan
Pratik Shah
College of Engineering and Computing Daniel Wehrung
Florida International University Department of Pharmaceutical Sciences
Miami, Florida Northeast Ohio Medical University
Rootstown, Ohio
Qiwen Shi
Department of Pharmaceutical Sciences Mingsheng Xu
College of Pharmacy Department of Polymer Science and
Northeast Ohio Medical University Engineering
Rootstown, Ohio Zhejiang University
Zhejiang, China
Huanxing Su
Li-Hao Young
State Key Laboratory of Quality Research in
Department of Occupational Safety
Chinese Medicine
and Health
and
School Public Health
Institute of Chinese Medical Sciences
China Medical University
University of Macau
Taichung, Taiwan
Macau SAR, China
and
Saijie Zhu
Interdisciplinary Laboratory for Nanoscale
College of Pharmacy
Science and Technology
The University of Texas at Austin
National Institute for Materials Science
Austin, Texas
Ibaraki, Japan
Xuena Zhu
Vijaykumar B. Sutariya College of Engineering and
College of Pharmacy Computing
University of South Florida Florida International University
Tampa, Florida Miami, Florida
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