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Biomedical Application
of Nanoparticles
 OXIDATIVE STRESS AND DISEASE

Series Editors

Lester Packer, PhD

Enrique Cadenas, MD, PhD
University of Southern California School of Pharmacy
Los Angeles, California

1. Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases,

edited by Luc Montagnier, René Olivier, and Catherine Pasquier
2. Understanding the Process of Aging: The Roles of Mitochondria, Free
Radicals, and Antioxidants, edited by Enrique Cadenas and Lester Packer
3. Redox Regulation of Cell Signaling and Its Clinical Application, edited by
Lester Packer and Junji Yodoi
4. Antioxidants in Diabetes Management, edited by Lester Packer, Peter Rösen,
Hans J. Tritschler, George L. King, and Angelo Azzi
5. Free Radicals in Brain Pathophysiology, edited by Giuseppe Poli, Enrique
Cadenas, and Lester Packer
6. Nutraceuticals in Health and Disease Prevention, edited by Klaus Krämer,
Peter-Paul Hoppe, and Lester Packer
7. Environmental Stressors in Health and Disease, edited by Jürgen Fuchs and
Lester Packer
8. Handbook of Antioxidants: Second Edition, Revised and Expanded,
edited by Enrique Cadenas and Lester Packer
9. Flavonoids in Health and Disease: Second Edition, Revised and Expanded,
edited by Catherine A. Rice-Evans and Lester Packer
10. Redox–Genome Interactions in Health and Disease, edited by Jürgen Fuchs,
Maurizio Podda, and Lester Packer
11. Thiamine: Catalytic Mechanisms in Normal and Disease States,
edited by Frank Jordan and Mulchand S. Patel
12. Phytochemicals in Health and Disease, edited by Yongping Bao and
Roger Fenwick
13. Carotenoids in Health and Disease, edited by Norman I. Krinsky,
Susan T. Mayne, and Helmut Sies
14. Herbal and Traditional Medicine: Molecular Aspects of Health, edited by
Lester Packer, Choon Nam Ong, and Barry Halliwell
15. Nutrients and Cell Signaling, edited by Janos Zempleni and
Krishnamurti Dakshinamurti
16. Mitochondria in Health and Disease, edited by Carolyn D. Berdanier
17. Nutrigenomics, edited by Gerald Rimbach, Jürgen Fuchs, and Lester Packer
18. Oxidative Stress, Inflammation, and Health, edited by Young-Joon Surh and
Lester Packer
Biomedical Application
of Nanoparticles

Edited by
Bertrand Henri Rihn
Université de Lorraine
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742

© 2018 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

Printed on acid-free paper

International Standard Book Number-13: 978-1-4987-5001-1 (Hardback)

This book contains information obtained from authentic and highly regarded sources. Reasonable efforts
have been made to publish reliable data and information, but the author and publisher cannot assume
responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize
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Library of Congress Cataloging‑in‑Publication Data

Library of Congress Cataloging-in-Publication Data

Names: Rihn, Bertrand, 1955- editor.
Title: Biomedical application of nanoparticles / editor, Bertrand Rihn.
Description: Boca Raton : Taylor & Francis, 2017. | Includes bibliographical references.
Identifiers: LCCN 2017010537 | ISBN 9781498750011 (hardback : alk. paper)
Subjects: | MESH: Nanoparticles | Nanotechnology--methods | Biocompatible
Materials | Biomedical Technology--methods
Classification: LCC R857.M3 | NLM QT 36.5 | DDC 610.28--dc23
LC record available at https://lccn.loc.gov/2017010537

Visit the Taylor & Francis Web site at

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Contents
Foreword....................................................................................................................ix
Series Preface: Oxidative Stress in Health and Disease............................................xi
Editor...................................................................................................................... xiii
Contributors.............................................................................................................. xv

Section I  Nanoparticle Characterization

Chapter 1 Nanoparticle World: History and Introduction to Their Diversity

in Medicine............................................................................................3
Annette B. Santamaria

Chapter 2 Dispersion and Characterization of Nanoparticles............................. 23

Didier Rouxel, Solenne Fleutot, and Van Son Nguyen

Chapter 3 Nanomedicine Clinical and Preclinical Use: A Status Report........... 53

Roudayna Diab, Sanghoon Kim, Ileana-Alexandra Pavel,
Nadia Canilho, Fernanda Bianca Haffner, Sijin Li,
Alain Celzard, Mihayl Varbanov, Emmanuel Lamouroux,
and Andreea Pasc

Chapter 4 Green Synthesis and Characterization of Semiconductor

and Metal Nanoparticles.....................................................................97
Sneha Bhagyaraj and Oluwatobi Samuel Oluwafemi

Section II  Interaction with Biological Systems

Chapter 5 The Nanoparticle “Coronome” Is Mainly Explained by InterPro

Domains of Proteins.......................................................................... 113
Olivier Joubert, Phèdre Rihn, and Bertrand Henri Rihn

Chapter 6 Nanoparticles and Viruses as Mitophagy Inducers in Immune

Cells................................................................................................... 133
Housam Eidi, Zahra Doumandji, Lucija Tomljenovic,
and Bertrand Henri Rihn

v
vi Contents

Section III  Safety Assessment for Human Use

Chapter 7 Rodent Inhalation Studies in Nanomaterial Risk Assessment.......... 163

Laurent Gaté, Frédéric Cosnier, and Flemming R. Cassee

Chapter 8 In Vivo Evaluation of the Hepatonephrotoxicity of Polymeric

Nanoparticles in Rats........................................................................ 189
Mosaad A. Abdel-Wahhab, Olivier Joubert,
Aziza A. El-Nekeety, Khaled G. Abdel-Wahhab,
Carole Ronzani, Ramia Safar, Ahmed A. El-Kady,
Nabila S. Hassan, Fathia A. Mannaa, and Bertrand Henri Rihn

Chapter 9 In Vitro Exposure Systems to Assess the Toxicity of Airborne

Substances.........................................................................................209
Tobias Krebs, Sonja Mülhopt, Silvia Diabaté,
Christoph Schlager, Hanns-Rudolf Paur, and Marco Dilger

Chapter 10 Nanoparticles as Nitroso-Glutathion Vehicles.................................. 223

Luc Ferrari, Roudayna Diab, Christophe Nemos, Ramia Safar,
and Chloe Puisney

Section IV Medical Use

Chapter 11 Transbarrier Trafficking of Nanoparticles: Perspectives
for Cancer Therapeutics.................................................................... 237
Lisa C. du Toit, Priyamvada Pradeep, Thashree Marimuthu,
Yahya E. Choonara, Pradeep Kumar, and Viness Pillay

Chapter 12 Polymeric Nanoparticles as a Vehicle for Delivery

of Antioxidants in the Brain: Potential Application
in Neurodegenerative Diseases......................................................... 277
Jean-Michel Rabanel, Ghislain Djiokeng-Paka,
and Charles Ramassamy

Chapter 13 Application of Nanomaterials in Photodynamic Therapy................ 301

Olayemi J. Fakayode, Ncediwe Tsolekile, Sandile P. Songca,
and Oluwatobi Samuel Oluwafemi
Contents vii

Chapter 14 Nanomedicine: A Complex Interplay between Patients, Science,

and Society........................................................................................ 313
Jean-Claude André, Jonathan Simon, and Bertrand Henri Rihn

Index....................................................................................................................... 323
http://taylorandfrancis.com
Foreword
Nanotechnology is a field of research and development that focuses on structures,
devices, and processes based on the atomic, molecular, or supramolecular modeling of
matter at scales typically of the order of one to one hundred nanometers (1–100 nm).
The constituents—sometimes referred to as elementary bricks—are nanomate-
rials that are produced only in small quantities. Nanomaterials include nanopar-
ticles, nanostructured coatings, dense bulk materials, and nanocomposites (with an
organic, inorganic, or metal matrix). These materials are expected to show novel
types of behavior due to the relative importance of quantum phenomena at this scale.
Many potential industrial and medical applications are emerging, and some nano-
materials are already in use. The European Commission estimated that the nano-
technology world market amounted to slightly over €40 billion in 2001. By 2008, the
global market for nanotechnology products is expected to top €700 billion. Between
2010 and 2015, the economic stakes via the advent of nanotechnology worldwide
are set to rise to €1,000 billion per year across all sectors (according to the National
Science Foundation) of which nanomaterials specifically account for almost €340
billion (Hitachi Research Institute). BCC Research (https://www.bccresearch.com​
/market-research/nanotechnology/nanocomposites-global-markets-nan021e.html)
estimated that in 2016, the nanocomposite market reached 333,043 metric tons and
$2.4 billion with an annual growth rate around 20% in both unit and value terms.
Over the same period, the nanotechnology industry is estimated to employ two to
three million people worldwide.
On the basis of such figures, many see the advent of nanosciences—nanotech-
nologies and nanomaterials—as a major turning point in twentieth and twenty-first
century industrial development. However, as in other industries, questions must be
asked about the introduction of these new products; notably, how to measure their
impact on health, the environment, and society. This is essential to guarantee the
responsible, safe, and controlled development of nanoscience applications.
The world nanoparticle market for biomedical, pharmaceutical, and cos-
metic applications was estimated at €85 million in 2000 (Rapport de la Direction
Générale de l’Industrie, des Technologies de l’Information et des Postes, 2004) and
reached €126 million in 2005 (i.e., an average yearly growth rate of 8.3%). This
market concerns inorganic particles used in the production of antimicrobial agents,
biological markets for research and diagnosis, biomagnetic separation, drug carriers,
MRI contrast medium, and in orthopedic devices and sunscreens. As reported by
the European Technology Platform (ETP) on Nanomedicine, nanomedicine has the
potential to enable early detection and prevention and to drastically improve diagno-
sis, treatment, and follow-up of many diseases, including cancer. Overall, the ETP on
Nanomedicine has identified more than 70 products under clinical trial that cover all
major diseases, including cardiovascular, neurodegenerative, musculoskeletal, and
inflammatory, as well as enable technologies in all healthcare areas. Nanomedicine
has been reported to account for 77 marketed products, ranging from nanodelivery
(44) and pharmaceutical (18) to imaging, diagnostics, and biomaterial (15).

ix
x Foreword

Taking into account such developments of nanomaterials, nanoparticles, and

nanodevices in the fields of medical application, and including nanomedicine as an
offshoot of nanotechnology, Biomedical Applications of Nanoparticles was written to
report on the exploration of nanoparticles. It includes reporting on their chemical and
physical properties, with a focus on description of the various types of nanoparticles,
how they can be synthesized, and their interaction in biological systems with proteins,
immune system, and targeted cells. Risk assessment of nanoparticles for humans is
also described, including cellular paradigms, transcriptomics, and toxicogenom-
ics, and provides guidance on safe use of nanoparticles. Finally, the application of
nanoparticles in medicine and antioxidant regenerative therapeutics are presented
in several chapters, with emphasis on how nanoparticles enhance transport of drugs
across biological membrane barriers and therefore may enhance drug bioavailability.
The book explores the following aspects in respect to the elements previously
discussed:

• In Section I, titled Nanoparticle Characterization, the following points

will be discussed. Nanoparticle world: a history and introduction to the
diversity, dispersion, and characterization of nanoparticles. Manufacturing
nanoparticles: A pharmacist’s approach, green synthesis, and characteriza-
tion of semiconductor and metal nanoparticles.
• In Section II, titled Interaction with Biologicial Systems, nanoparticle inter-
action with proteins and the corona formation will be described as well
as the question of the nanoparticle and virus as mitophagy inducers in
immune cells.
• In Section III, titled Safety Assessment for Human Use, attention will be
paid to rodent inhalation in nanoparticle risk assessments, in vivo hepa-
toxicity nephrotoxicity of polymeric nanoparticles, and in vitro exposure
systems of nanoparticles.
• In Section IV, medical use is detailed in relation to some particular behav-
iors of nanoparticules, that is, the transbarrier trafficking of nanoparticles
in perspectives for cancer therapeutics, the involvement of nanoparticles
as a vehicle of antioxidants in diseases, the application of nanoparticles in
photodynamic therapy, and the use of nanoparticles as nitroso-glutathion
vehicles.

As emphasized by the ETP and described in the various sections of this book,
nanomedicine is a key enabling instrument for personalized, targeted, and regenera-
tive medicine by delivering the next level of drugs, treatments, and implantable devices
to clinicians and patients for real breakthroughs in healthcare. Beyond that, nanomedi-
cine provides important new tools to deal with the grand challenge of an aging popula-
tion and is thought to be instrumental for improved and cost-­effective healthcare—a
crucial factor for making medicine and treatment available and affordable to all.

Dr. Eric Gaffet

Institut Jean Lamour
UMR 7198 Centre National de Recherche Scientifique—Université de Lorraine
Series Preface: Oxidative
Stress in Health and Disease
Oxidative stress is an underlying factor in health and disease. In this series of books,
the importance of oxidative stress and disease associated with cell and organ sys-
tems of the body is highlighted by exploring the scientific evidence and the clinical
applications of this knowledge. This series is intended for researchers in the bio-
medical sciences, clinicians, and all persons with an interest in the health sciences.
The potential of such knowledge for healthy development, healthy aging, and disease
prevention warrants further knowledge about how oxidants and antioxidants modu-
late cell and tissue function.
Bertrand Rihn is to be congratulated for producing this very excellent and timely
book, Biomedical Application of Nanoparticles, in the ever-growing field of impor-
tance of the application of nanoparticle technology as a vehicle to deliver nutrients
and pharmaceuticals for human health.

Lester Packer
Enrique Cadenas
Oxidative Stress and Disease Series Editors

xi
http://taylorandfrancis.com
Editor
Bertrand Henri Rihn, MD, DSc, professor of biochemistry and molecular biol-
ogy at Lorraine University, France, is a leading expert in the field of particulate
toxicology, with research topics including safety toxicology, immunotoxicology,
and investigating the transcriptomic changes in macrophages following nanopar-
ticle exposure. In addition to his research, Professor Rihn has also worked as a
clinical toxicologist, and was awarded the Baratz Award (2004) and the E. Taub
Award (2011) from the National Academy of Medicine (France). He also served as
the president of the French Society of Toxicology from 2007 to 2009, and was a
EUROTOX Registered Toxicologist.

xiii
http://taylorandfrancis.com
Contributors
Khaled G. Abdel-Wahhab Alain Celzard
Medical Physiology Department Institut Jean Lamour
National Research Center UMR 7198–Centre National de
Cairo, Egypt Recherche Scientifique—Université
de Lorraine
Mosaad A. Abdel-Wahhab Épinal, France
Food Toxicology and Contaminants
Department Yahya E. Choonara
National Research Center Wits Advanced Drug Delivery Platform
Cairo, Egypt Research Unit
Department of Pharmacy and
Jean-Claude André Pharmacology
CNRS School of Therapeutic Sciences
Nancy, France Faculty of Health Sciences
University of the Witwatersrand
Sneha Bhagyaraj Johannesburg, South Africa
Centre for Nanomaterials Science
Research Frédéric Cosnier
University of Johannesburg Institut National de Recherche et de
Doornfontein, South Africa Sécurité
Département Toxicologie et
Nadia Canilho Biométrologie
SRSMC UMR 7565 Vandœuvre-lès-Nancy, France
Université de Lorraine–Centre National
de Recherche Scientifique Roudayna Diab
Vandœuvre-lès-Nancy, France SRSMC UMR 7565
Université de Lorraine–Centre National
Flemming R. Cassee de Recherche Scientifique
National Institute for Public Health and Vandœuvre-lès-Nancy, France
the Environment
Bilthoven, the Netherlands Silvia Diabaté
Karlsruhe Institute of Technology
and
(KIT)
Institute for Risk Assessment Studies Institute of Toxicology and Genetics
Utrecht, the Netherlands Eggenstein-Leopoldshafen, Germany

xv
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