Nanomaterials in Drug Delivery, Imaging,

and Tissue Engineering

Scrivener Publishing 100 Cummings Center, Suite 541J

Beverly, MA 01915-6106

Publishers at Scrivener Martin Scrivener (martin@scrivenerpublishing.com)

Phillip Carmical (pcarmical@scrivenerpublishing.com)

Nanomaterials in Drug Delivery,

Imaging, and Tissue Engineering

Edited by

Ashutosh Tiwari and Atul Tiwari

# >

sfcriv Publi

WILEY

Scrivener Publishing

Copyright © 2013 by Scrivener Publishing LLC. All rights reserved.

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Library of Congress Cataloging-in-Publication Data:

ISBN 978-1-118-29032-3

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

Contents

Preface xv List of Contributors xix

Part I: Biomedical Nanomaterials 1 Nanoemulsions: Preparation, Stability and Application

in Biosciences 3 Thomas Delmas, Nicolas Atrux-Tallau, Mathieu Goutayer, SangHoon Han, Jin Woong Kim, and Jerome Bibette 1.1 Introduction 4 1.2 Nanoemulsion: A Thermodynamic Definition

and Its Practical Implications 7 1.2.1 Generalities

vi CONTENTS

1.5 Interactions between Nanoemulsions and the Biological Medium: Applications in Biosciences 37 1.5.1 Nanoemulsion Biocompatibility 37 1.5.2 Classical Targeting Approach by Chemical

Grafting - Example of Tumor Cell Targeting by cRGD Peptide for Cancer Diagnosis and Therapy 40

1.5.3 New 'No Synthesis Chemistry' Approach -Example of Pal-KTTKS and Asiaticoside Targeting for Cosmetic Actives Delivery 43

1.5.4 Conclusion on Nanoemulsions Application in Biosciences 48

1.6 General Conclusion 49 References 50

Multifunctional Polymeric Nanostructures for Therapy and Diagnosis 59 Angel Contreras-Garcia and Emilio Bucio

2.1 Introduction 60 2.2 Polymeric-based Core-shell Colloid 63 2.3 Proteins and Peptides 66 2.4 Drug Conjugates and Complexes

with Synthetic Polymers 67 2.5 Dendrimers, Vesicles, and Micelles 69

2.5.1 Dendrimers 69 2.5.2 Vesicles 70 2.5.3 Micelles 72

2.6 Smart Nanopolymers 73 2.6.1 Temperature and pH Stimuli-responsive

Nanopolymers 74 2.6.2 Hydrogels 74 2.6.3 Stimuli Responsive Biomaterials 75 2.6.4 Interpenetrating Polymer Networks 76

2.7 Stimuli Responsive Polymer-metal Nanocomposites 77 2.8 Enzyme-responsive Nanoparticles 80 2.9 Carbon Nanotubes 81

2.10 Hybrid Polymeric Nanomaterials 83 Acknowledgements 85 References 85

2

CONTENTS vii

Carbon Nanotubes: Nanotoxicity Testing and Bioapplications 99 R. Sharma and S. Kwon 3.1 Introduction 100

3.1.1 What is Nanotoxicity of Nanomaterials? 100 3.1.2 Historical Review of Carbon Nanotube 101 3.1.3 Carbon Nanotubes (CNTs) and Other

Carbon Nanomaterials 102 3.1.4 Physical Principles of Carbon Nanotube

Surface Science 104 3.1.5 Motivation - Combining Nanotechnology

and Surface Science with Growing Bioapplications 106

3.2 Cytotoxicity Measurement and Mechanisms of CNT Toxicity 113 3.2.1 In Vivo Studies on CNT Toxicity 115 3.2.2 Inflammatory Mechanism of CNT Cytoxicity 116 3.2.3 Characterization and Toxicity of

SWCNT and MWCNT Carbon Nanotubes 118 3.3 MSCs Differentiation and Proliferation

on Different Types of Scaffolds 122 3.3.1 An In Vivo Model CNT-Induced

Inflammatory Response in Alveolar Co-culture System 124

3.3.2 Static Model: 3-Dimensional Tissue Engineered Lung 126

3.3.3 Dynamic Model: Integration of 3D Engineered Tissues into Cyclic Mechanical Strain Device 128

3.3.4 In Vivo MR Microimaging Technique of Rat Skin Exposed to CNT 129

3.3.5 New Lessons on CNT Nanocomposites 132 3.3.6 Development of a 3D Collagen Scaffold

Coated with Multiwalled CNT Nanomaterials in Bone Regeneration 135

3.4 Conclusions 137 Acknowledgements 138 References 138

3

viii CONTENTS

Part II: Advanced Nanomedicine 4 Discrete Metalla-Assemblies as Drug Delivery Vectors 147

Bruno Therrien 4.1 Introduction 147 4.2 Complex-in-a-Complex Systems 148 4.3 Encapsulation of Pyrenyl-functionalized Derivatives 153 4.4 Exploiting the Enhanced Permeability

and Retention Effect 157 4.5 Incorporation of Photosensitizers

in Metalla-assemblies 160 4.6 Conclusion 163

Acknowledgments 163 References 164

5 Nanomaterials for Management of Lung Disorders and Drug Delivery 167 Jyothi U. Menon, Aniket S. Wadajkar, Zhiwei Xie, and Kytai T. Nguyen 5.1 Lung Structure and Physiology 168 5.2 Common Lung Diseases and Treatment Methods 169

5.2.1 Lung Cancer 169 5.2.2 Pulmonary Arterial Hypertension 170 5.2.3 Obstructive Lung Diseases 171

5.3 Types of Nanoparticles (NPs) 171 5.3.1 Liposomes 172 5.3.2 Micelles 174 5.3.3 Dendrimers 175 5.3.4 Polymeric Micro/Nanoparticles 175

5.4 Methods for Pulmonary Delivery 177 5.4.1 Nebulization 177 5.4.2 Metered Dose Inhalation (MDI) 180 5.4.3 Dry Powder Inhalation (DPI) 181 5.4.4 Intratracheal Administration 181

5.5 Targeting Mechanisms 182 5.5.1 Passive Targeting 182 5.5.2 Active Targeting 183 5.5.3 Cellular Uptake Mechanisms 186

5.6 Therapeutic Agents Used for Delivery 186 5.6.1 Chemotherapeutic Agents 186 5.6.2 Bioactive Molecules 188 5.6.3 Combinational Therapy 188

CONTENTS ix

5.7 Applications 189 5.7.1 Imaging/Diagnostic Applications 189 5.7.2 Therapeutic Applications 191 5.7.3 Lung Remodeling and Regeneration 192

5.8 Design Considerations of NPs 193 5.8.1 Half-life of NPs 193 5.8.2 Drug Release Mechanisms 193 5.8.3 Clearance Mechanisms in the Lung 194

5.9 Current Challenges and Future Outlook 195 References 196

6 Nano-Sized Calcium Phosphate (CaP) Carriers for Non-Viral Gene/Drug Delivery 203 Donghyun Lee, Geunseon Ahn and Prashant N. Kumta 6.1 Introduction 204 6.2 Vectors for Gene Delivery 206

6.2.1 Viral Vectors 207 6.2.2 Non-viral Vectors 207 6.2.3 Calcium Phosphate Vectors 209

6.3 Modulation of Protection and Release Characteristics of Calcium Phosphate Vector 217

6.4 Calcium Phosphate Carriers for Drug Delivery Systems 223 6.4.1 Antibiotics Delivery 223 6.4.2 Growth Factor Delivery 225

6.5 Variants of Nano-calcium Phosphates: Future Trends of the CaP Delivery Systems 225 Acknowledgements 227 References 227

Part III: N a n o t h e r a g n o s t i c s

7 Organics Modified Mesoporous Silica for Controlled Drug Delivery Systems 239 Jingke Fu, Yang Zhao, Yingchun Zhu and Fang Chen 7.1 Introduction 239

x CONTENTS

7.2 Controlled Drug Delivery Systems Based on Organics Modified Mesoporous Silica 7.2.1 MSNs-based Drug Delivery Systems

Controlled by Physical Stimuli 7.2.2 MSNs-based Drug Delivery Systems

Controlled by Chemical Stimuli Conclusions References

240

244

252 264 265

7.3

Responsive Polymer-Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery 269 Weitai Wu and Shuiqin Zhou 8.1 Introduction 270 8.2 Mechanisms of Response 274

8.2.1 Reception of an External Signal 274 8.2.2 Volume Phase Transition of

the Hybrid Nanogels 281 8.2.3 Transduction of the Volume Change

into an Optical Signal 286 8.2.4 Regulated Drug Delivery 288

8.3 Synthesis of Responsive Polymer-inorganic Hybrid Nanogels 291 8.3.1 Synthesis of the Hybrid Nanogels from

Pre-synthesized Polymer Nanogels 291 8.3.2 Synthesis of the Hybrid Nanogels from

Pre-synthesized Inorganic NPs 295 8.3.3 Synthesis of the Hybrid Nanogels by

a Heterogeneous Polymerization Method 298 8.4 Applications 299

8.4.1 Responsive Polymer-inorganic Hybrid Nanogels in Optical Sensing 299

8.4.2 Responsive Polymer-inorganic Hybrid Nanogels in Diagnostic Imaging 305

8.4.3 Responsive Polymer-inorganic Hybrid Nanogels in Drug Delivery 307

References 312

8

CONTENTS

Core/Shell Nanoparticles for Drug Delivery and Diagnosis 321 Hzvanbum Lee, Jae Yeon Kim, Eun Hee Lee, Young In Park, Keun Sang Oh, Kwangmeyung Kim, Ick Chan Kwon and Soon Hong Yuk 9.1 Introduction 321 9.2 Core/Shell NPs from Polymeric Micelles 325

9.2.1 Polymeric Micelles with Physical Drug Entrapment 325

9.2.2 Polymeric Micelles with Drug Conjugation 327 9.2.3 Polymeric Micelles Formed by

Temperature-induced Phase Transition 329 9.3 Phospholipid-based Core/Shell Nanoparticles 331 9.4 Layer-by-Layer-Assembled Core/Shell

Nanoparticles 335 9.5 Core/Shell NPs for Diagnosis 336 9.4 Conclusions 337

Acknowledgments 337 References 337

Dendrimer Nanoparticles and Their Applications in Biomedicine 345 Arghya Paul, Wei Shao, Tom J. Burdon, Dominique Shum-Tim and Satya Prakash 10.1 Introduction 346 10.2 Dendrimers and Their Characteristics 347 10.3 Biomolecular Interactions of

Dendrimer Nanocomplexes 349 10.3.1 Genes (siRNA/ANS/DNA) 350 10.3.2 Drugs and Pharmaceutics 351

10.4 Potential Applications of Dendrimer in Nanomedicine 353 10.4.1 Delivery of Chemotherapeutics 353 10.4.2 Delivery of Biomolecules 354 10.4.3 Imaging 356

10.5 Conclusion 359 Acknowledgements 361 Indexing Words 361 References 361

9

10

ix

xii CONTENTS

11 Theranostic Nanoparticles for Cancer Imaging and Therapy 369 Matni Murakami, Mark J. Ernsting and Shyh-Dar Li 11.1 Introduction 369 11.2 Multifunctional Nanoparticles for Noninvasive

Monitoring of Biodistribution 372 11.2.1 Radiolabeled Nanoparticles 372 11.2.2 Fluorescence Imaging

of Biodistribution 373 11.2.3 Multimodal Radiolabel and Fluorescence

Imaging of Biodistribution 374 11.2.4 MRI Imaging of Biodistribution 375 11.2.5 Multimodal MRI and Fluorescence

Imaging of Biodistribution 377 11.2.6 Multimodal Optical and CT Imaging of

Biodistribution 378 11.2.7 Pharmacokinetics and Pharmacodynamics

of Theranostics vs. Diagnostics 379 11.3 Multifunctional Nanoparticles

for Monitoring Drug Release 381 11.3.1 MRI Imaging of Drug Release 381 11.3.2 Fluorescent Imaging of Drug Release 385

11.4 Theranostics to Image Therapeutic Response 386 11.5 Conclusion and Future Directions 388

Acknowledgement 389 References 389

Part IV: Nanoscaffolds Technology

12 Nanostructure Polymers in Function Generating Substitute and Organ Transplants 397 S.K. Shukla 12.1 Introduction 397 12.2 Important Nanopolymers 399

12.2.1 Hydrogels 401 12.2.2 Bioceramics 402 12.2.3 Bioelastomers 403 12.2.4 Chitosan and Derivatives 404 12.2.5 Gelatine 404

CONTENTS xiii

12.3 Medical Applications 405 12.3.1 Tissue Engineering for

Function Generating 406 12.3.2 Tissue Engineering in Artificial Heart 408 12.3.3 Tissue Engineering in Nervous System 409 12.3.4 Bone Transplants 412 12.3.5 Kidney and Membrane Transplants 414 12.3.6 Miscellaneous 417

12.4 Conclusion 419 Acknowledgement 419 References 419

Electrospun Nanofiber for Three Dimensional Cell Culture 425 Yashpal Sharma, Ashutosh Tizvari and Hisatoshi Kobayashi 13.1 Introduction 425 13.2 Nanofiber Scaffolds Fabrication Techniques 427

13.2.1 Self-assembly 427 13.2.2 Phase Separation 428 13.2.3 Electrospinning 429

13.3 Parameters of Electrospinning Process 431 13.3.1 Viscosity or Concentration of the

Polymeric Solution 431 13.3.2 Conductivity and the Charge Density 432 13.3.3 Molecular Weight of Polymer 433 13.3.4 Flow Rate 433 13.3.5 Distance from Tip to Collector 433 13.3.6 Voltage Applied 433 13.3.7 Environmental Factors 434

13.4 Electrospun Nanofibers for Three-dimensional Cell Culture 434

13.5 Conclusions 437 References 438

Magnetic Nanoparticles in Tissue Regeneration 443 Anuj Tripathi, Jose Savio Melo and Stanislaus Francis D'Souza 14.1 Introduction 443 14.2 Magnetic Nanoparticles: Physical Properties 446 14.3 Synthesis of Magnetic Nanoparticles 448

13

14

xiv CONTENTS

14.4 Design and Structure of Magnetic Nanoparticles 451 14.5 Stability and Functionalization of

Magnetic Nanoparticles 453 14.6 Cellular Toxicity of Magnetic Nanoparticles 458 14.7 Tissue Engineering Applications of Magnetic

Nanoparticles 461 14.7.1 Magnetofection 463 14.7.2 Cell-patterning 466 14.7.3 Magnetic Force-induced Tissue Fabrication 469

14.8 Challenges and Future Prospects 481 Acknowledgement 482 References 482

15 Core-sheath Fibers for Regenerative Medicine 493 Rajesh Vasita and Fabrizio Gelain 15.1 Introduction 494

15.1.1 Tissue Engineering 495 15.1.2 Scaffold Fabrication Technology 496

15.2 Core-sheath Nanofiber Technology 497 15.2.1 Co-axial Electrospinning 499 15.2.2 Emulsion Electrospinning 509 15.2.3 Melt Co-axial Electrospinning 511

15.3 Application of Core-sheath Nanofibers 512 15.3.1 Delivery of Bioactive Molecules 512 15.3.2 Tissue Engineering 521

15.4 Conclusions 527 References 527

Index 535

Preface

The ability to control the structure of materials has scientists geared up to accomplish what once appeared impossible before the advent of nanotechnology. Now is an auspicious time to generate nano-scopic self-assembled and self-destructive robots for effective utili-zation in therapeutics, diagnostics and biomedical implants.

Therapeutic drugs encapsulated in precisely fabricated lipid-based nanocarriers can be used in imaging and drug delivery. Chapter 1, "Nanoemulsions: Preparation, Stability and Application in Biosciences," describes the application of such techniques in the pharmaceutical and cosmetic industries. Available synthetic routes help in the development of polymeric materials for potential use in biomedical applications. Chapter 2, "Multifunctional Polymeric Nanostructures for Therapy and Diagnosis," describes the fabrica-tion of tuneable polymers by both conventional chemical methods and sophisticated processes (i.e., surface modification) using ioni-zing radiation. Because synthetic materials are often associated with toxic side effects they need to be regulated. The cytoxicity and inflammatory responses of such engineered nanomaterials are investigated in Chapter 3, "Carbon Nanotubes: Nanotoxicity Testing and Bioapplications." An overview of novel metalla-assemblies as drug carriers is presented in Chapter 4, "Discrete Metalla-Assemblies as Drug Delivery Vectors." Notable advantages and limitations of metalla-assemblies are assessed from a biological point of view.

Chapter 5, "Nanomaterials for Management of Lung Disorders and Drug Delivery" summarizes different types of nanoparticles currently available for pulmonary drug delivery. Various mecha-nisms and challenges in inhalational drug delivery technologies are also discussed in this chapter. A thrust towards the develop-ment of novel nanoparticles paved the way for successful cancer diagnosis and treatment. Gene therapy for curing multiple inheri-ted and/or acquired diseases has become an active area of research

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xvi PREFACE

and development. The use of bioceramics as vehicular media for gene delivery is investigated in Chapter 6, "Nano-sized Calcium Phosphate Carriers for Non-viral Gene/Drug Delivery." Chapter 7, "Organics Modified Mesoporous Silica for Controlled Drug Delivery Systems," details the use of mesoporpous silica as a stimuli-res-ponsive drug delivery vehicle. Chapter 8, "Responsive Polymer-Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery," analyzes the recent advancements in responsive poly-mer-inorganic hybrid nanogels.

Nanoparticle fabrication techniques that produce hydrophilic core/shell and incorporate hydrophobic drugs offer conside-rable advantages for diagnosis and therapy. Chapter 9, "Core/ Shell Nanoparticles for Drug Delivery and Diagnosis," focuses on nanomedicine for tumor-targeting stimulated release of proteins and their cancer imaging capabilities. On the other hand, dendri-metric network polymer nanoparticles offer certain advantages not available in other materials. Their high surface functionalities provide an opportunity to modify an outer surface and achieve multivalent effects. Chapter 10, "Dendrimer Nanoparticles and Their Applications in Biomedicine," explores the unique features of this nanomaterial for their successful future applications as bio-therapeutics. Chapter 11, "Theranostic Nanoparticles for Cancer Imaging and Therapy," presents advantages and limitations in the development of nanoparticles for cancer theranostics along with recent progress in the field

Biocompatible polymeric architecture has gained significant attention in scaffolds for their use in tissue regeneration, tissue adhesives, hemostats, and transient barriers for tissue adhesion. Chapter 12, "Nanostructure Polymers in Function Generating Substitute and Organ Transplants," highlights various nanoengi-neerd polymeric materials that are being utilized in function gene-rating substitutes and organ transplants. Similarly, nanofibrous scaffolds are widely studied for tissue engineering. Chapter 13, "Electrospun Nanofiber for Three Dimensional Cell Culture," describes the fabrication and interesting properties of electros-pun nanofiber matrices. An overview on the progress of magnetic nanoparticles for cell-directed tissue engineering and regenerative medicine is presented in Chapter 14, "Magnetic Nanoparticles In Tissue Regeneration." The fabrication of core-sheath nanofibers and its application in regenerative medicine is discussed in Chapter 15, "Core-Sheath Fibers for Regenerative Medicine." Magnetic particles

PREFACE xvii

are gaining momentum for their use in three-dimensional tissue generation.

This book is written for a large readership including university students and researchers from diverse backgrounds such as chem-istry, materials science, physics, pharmacy, medical science, and biomedical engineering. It can be used not only as a textbook for both undergraduate and graduate students, but also as a review and reference book for researchers in materials science, bioengi-neering, biotechnology, nanotechnology and the medical and phar-maceutical fields. We hope this book provides the reader valuable insight into the major areas of biomedical nanomaterials, advanced nanomedicine, nanotheragnostics and cutting-edge nanoscaffolds. The interdisciplinary nature of the topics in this book will help both young researchers and senior academicians. We are grateful to Martin Scrivener for giving us the opportunity to publish a book on a subject of such high scientific curiosity and importance.

Editors Ashutosh Tiwari, PhD

Atul Tiwari, PhD January 1, 2013

List of Contributors

Genseon Ahn received his BS degree in mechanical engineering at Soongsil University, Republic of Korea, in 2008, and MS degree in mechanical engineering at Pohang University of Science and Technology (POSTECH) in 2010. Currently, Mr. Ahn is a researcher at Chung-Ang has University studying tissue engineered scaffold fabrication using natural and synthetic polymers. Mr. Ahn pub-lished has 5 articles, participated in 15 conference presentations, and co-authored as 1 patent application.

Nicolas Atrux-Tallau is postdoctoral researcher at the ESPCI Paris Tech. He obtained his doctorate in skin biology and physiology with a pharmaceutical technologies background from the School of Pharmacy, University of Lyon, France. Dr Atrux-Tallau first skin research experience was in Dr. Howard I. Maibach team at UCSF and continues his research in the fields of dermatology, cosmetic and dermo-pharmacy

Jerome Bibette is professor and director of the LCMD Laboratory at Ecole Superieure de Physique et Chimie Industrielles (ESPCI), Paris. His research interest lies in colloids: their preparation, sta-bility, phase transition properties and use in biotechnologies. He is also founder of several companies like Ademtech, Raindance Technologies and Capsum. He has published about 120 papers, owns 45 patents, has been a member of the Institut Universitaire de France since 1994 and was awarded Silver Medal of CNRS in 2000.

Emilio Bucio graduated in chemical physics at the National University of Mexico in 1999 where he now works in the Nuclear Science Institute. His fields of expertise are radiation chemistry, fluorinated polymers, and synthesis of smart polymers. Awards Medal "Gustavo Baz Prada" in 1993, Medal "Alfonso Caso" in 1999, and LAS/ANS award for best publication of the year in 2010

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xx LIST OF CONTRIBUTORS

by Nuclear American Society Latinoamerican Section. He has pub-lished 71 articles in international journals.

Tom J Burdon is an undergraduate student working on stem cell therapy, regenerative medicine and nanodelivery systems as a part of his co-op program in Biomedical Engineering Department, McGill University. His research interest includes stem cells, poly-mer chemistry and biomedicine.

Fang Chen received a BS in materials science and engineering from The Southeast University in 2008 and an MS in materials sci-ence from Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS) in 2011. Her research focused on synthesizing of pH-sensitive controlled-release drug delivery systems.

Angel Contreras-Garcia earned his PhD in 2010 at the National University of Mexico is currently a postdoctoral researcher at Ecole Polytechnique, Montreal. He has published 11 articles and 4 chap-ters in books related to biomaterials to be applied in the medical field, using non-conventional chemical methods to synthesize polymers.

S.F. D'Souza is currently the associate director of the Biomedical Group and also Head, Nuclear Agriculture and Biotechnology Division, at Bhabha Atomic Research Centre, Mumbai, India, where he coordinates institutional programs on food, agriculture and biotechnology. He is also senior professor at the Homi Bhabha National Institute. He has a PhD in Biochemistry and his major research interest has been in the field of enzymes and microbial technology with special reference to immobilized cells for use in bioprocessing, biosensors, bioremediation and nanotechnology. He has to his credit more than 200 scientific papers and invited reviews in reputed international journals.

Thomas Delmas is a PhD R&D project manager at Capsum, in charge of 2 innovative technological platforms based on nanoemul-sions and milifluidics for encapsulation and drug delivery. His research interest lies in research at the interfaces between chemical physics and biology, from cancer diagnosis and therapy, to cosmet-ics and dermo-pharmacy, having published about 10 publications and 6 patents in these fields.

LIST OF CONTRIBUTORS xxi

Mark Ernsting received his PhD from the University of Toronto and is a senior biomedical engineer at the Ontario Institute for Cancer Research. Mark specializes in the design and preclinical evaluation of drug delivery systems, with an emphasis on polymeric materi-als, and has published 13 papers in this field.

Jingke Fu is currently a PhD student at the Key Laboratory of Inorganic Coating Materials at the Shanghai Institute of Ceramics, Chinese Academy of Sciences, PR. China. Her research focuses on mesoporous silica nanomaterials based stimuli-responsive delivery systems.

Mathieu Goutayer completed a PhD in chemical physics at the University of Paris VI, France in 2008. He joined Capsum in 2009 where he is responsible for a group focused on the design and development of new encapsulation systems, using microfluidics for perfume and cosmetic products. Dr Goutayer owns more than 15 patents in the fields of encapsulations.

Sang-Hoon Han is the director of Cosmetic & Personal Care Research Institute of Amore-Pacific R&D Center. He received his PhD in polymer science and engineering at Sungkyunkwan University in 2010. His research interest lies in developing novel cosmetic formulations from emulsions, gels, and vesicles. He has published 22 international papers about cosmetics.

Jae Yeon Kim is a graduate student at the College of Pharmacy at Korea University. He received his BS degree from the Department of Biology Education at Korea National University of Education in 2007. His work includes the design and development of sustained delivery system for protein-based drug using nanoparticles.

Jin Woong Kim is an associate professor of applied chemistry at Hanyang University. He earned his PhD in 2000 in industrial chemis-try from the Hanyang University. His current research involves devel-oping new techniques to fabricate functional soft materials with novel structures. He has more than 130 publications in his research field.

Kwangmeyung Kim is a principle research scientist at the Center for Theragnosis in Korea Institute of Science and Technology (KIST). He received his PhD degree in 2003 from the Department of

xxii LIST OF CONTRIBUTORS

Materials Science and Engineering at Gwangju Institute of Science and Technology (GIST), Korea. He joined KIST and developed cancer-specific optical imaging systems. His research focuses on noninvasive cancer-specific molecular imaging and therapeutic/ diagnostic nanoprobes; he develops smart nanoplatform technol-ogy for future diagnosis and therapy of various diseases.

Hisatoshi Kobayashi is group leader of Biofunctional Materials at Biomaterials Centre, National Institute for Materials Science, Japan. He has published more than 150 publications, books and patents in the field of biomaterials science and technology as well as edited/authored three books on the advanced state-of-the-art of biomaterials.

Prashant Kumta is Edward R. Weidlein Chair Professor at University of Pittsburgh; was Professor at Carnegie Mellon University for 17 years; and is Editor in Chief of Materials Science and Engineering, B, Advanced Functional Solid-State Materials. His interests are in elec-trochemical, electronic, bone tissue engineering, biomineralization, and non-viral gene delivery applications.

Ick Chan Kwon is the Head of the Center for Theragnosis in Korea Institute of Science and Technology (KIST). He received his PhD in 1993 in pharmaceutics and pharmaceutical chemistry from the University of Utah in 1993. He serves as the president of the Korean Society of Molecular Imaging, as an Associate Editor of the Journal of Controlled Release, as an Asian Editor of the Journal of Biomedical Nanotechnology, and as a member of several journal editorial boards. His current research interests are targeted drug delivery with poly-meric nanoparticles and the development of smart nanoplatforms for theranosis.

Soonjo Kwon is MS and PhD in biological engineering from the University of California-Irvine and is serving as faculty at Utah State University, Logan, USA. He is decorated with university aca-demic honors and serves as the Director of the Institute of Biological Engineering, Utah.

Donghyun Lee obtained his Bachelor of Engineering in materi-als science and engineering from Korea University, Seoul, Korea in 2002 and his MS degree materials science and engineering and

LIST OF CONTRIBUTORS xxiii

PhD in biomedical Engineering from Carnegie Mellon University in 2004 and 2009 respectively. He recently joined the Department of Biomedical Engineering at Chung-Ang University as an assis-tant professor, after serving as a post-doctoral research associate at the University of Pittsburgh. His main research interests are in the synthesis, structure and properties of nanostructured materi-als for tissue engineering and non-viral gene delivery applications. He has given 12 invited and poster presentations and is the author and co-author of 11 refereed publications.

Eun Hee Lee is a professor at the College of Pharmacy, Korea University. She received her PhD from the Department of Industrial and Physical Pharmacy at Purdue University in 2007 where she also worked as a postdoctoral fellow from 2007 to 2010. Her current research interests are the solid state chemistry and crystallization.

Hwanbum Lee is a graduate student at the College of Pharmacy, Korea University. He received his BS degree from the Department of Advanced Material Chemistry at Korea University in 2010. His work includes the design and development of molecular imaging probes and therapeutic agents using nanoparticles.

Shyh-Dar Li is a principal investigator at the Ontario Institute for Cancer Research focusing on nanomedicine research. He has pub-lished 22 peer-reviewed articles over the last five years and received research funding from major agencies, including Prostate Cancer Foundation, Canadian Institutes of Health Research and National Cancer Institute.

J.S. Melo obtained his PhD in biochemistry in 1990 from Mumbai University, India. Currently, he is a senior scientific officer of the Nuclear Agriculture & Biotechnology Division at Bhabha Atomic Research Centre, Mumbai, India, and is also an associate professor at the Homi Bhabha National Institute. He has developed a number of novel techniques for immobilization of enzymes and cells. His current field of interest is bioremediation, nanoscience and sensors. He has to his credit 30 publications in international journals.

Jyothi Menon is a PhD student in bioengineering, the University of Texas at Arlington. She received her MS in bioengineering, UT Arlington in 2010. Jyothi's research interests include nanoparticulate

xxiv LIST OF CONTRIBUTORS

drug delivery systems, biomaterials and tissue engineering. She has authored 4 journal papers and is the recipient of William L. and Martha Hughes award'09 and Provost's level Enhanced Graduate Teaching Assistantship and Fellowship at UT Arlington.

Mami Murakami received her PhD under the supervision of Prof. Kataoka from the University of Tokyo in 2009. Currently, she is working with Dr. Li at Ontario Institute for Cancer Research with a postdoctoral fellowship. Her main interest concerns the nanode-vices for cancer therapy.

Kytai T. Nguyen is an associate professor in the Department of Bioengineering, the University of Texas at Arlington and The University of Texas Southwestern Medical Center, Dallas. She received her PhD in chemical engineering with an emphasis in bioengineering at Rice University in 2000. Dr. Nguyen's research interests are in the field of nanotechnology for drug and/or gene delivery systems, cellular, and tissue engineering. Her group has produced more than 40 peer-reviewed manuscripts, 3 patent appli-cations, 5 book chapters, and numerous conference abstracts and papers

Keun Sang Oh is a research professor at the College of Pharmacy, Korea University. He received his PhD from the Department of Advanced Materials at Hannam University in 2009. He then joined the Center for Theragnosis in Korea Institute of Science and Technology (KIST) as a postdoctoral fellow from 2009 to 2012. His current research interest is nanomedicine for effective diagnosis and therapy.

Young In Park is a professor at the College of Pharmacy, Korea University. He received his PhD in biochemistry at Indiana University in 1987. After the postdoctoral research at Indiana University, he joined the Department of Genetic Engineering as an assistant profes-sor in 1988. His current research interest lies on the development of antiallegic drug.

Arghya Paul received his MSc (A) in biotechnology and PhD in bio-medical engineering (Faculty of Medicine) from McGill University, Canada. His thesis work was based on developing new bio thera-peutic devices using stem cells and nanobiohybrid gene delivery

LIST OF CONTRIBUTORS XXV

vector systems for cardiovascular applications. Dr. Paul is currently a postdoctoral fellow in Prof. Ali Khademhosseini's laboratory at Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School. His research areas broadly include nanobiotech-nology, stem cell based bioengineering and biotherapeutic device for medical applications.

Satya Prakash is a Professor of Biomedical Engineering and Artificial Cells and Organs Research in the Faculty of Medicine at McGill University and works as director of McGill's Biomedical Technology and Cell Therapy Research Laboratory and member of physiology and experimental medicine department. He has pub-lished more than 225 peer reviewed research articles and abstracts, been listed as an inventor in 52 approved/pending patents. His primary research interest is developing several innovative research areas based of nanomedicine, artificial cells, probiotics, microen-capsulation, cell therapy, tissue engineering, medical device engi-neering, and other biomedical technology developments.

Wei Shao obtained her MSc in biochemistry from the Biochemistry department, McGill University. Currently, she is a PhD student in Prof. Prakash's Lab in Biomedical Engineering (Faculty of Medicine) in McGill University, Canada. Her thesis focuses on development targeted nano-delivery systems for genes and chemotherapy drugs for cancer treatment using nanomaterials including polymers, virus-like particles, and carbon nanotubes.

Rakesh Sharma has a PhD in biochemistry and MR imaging and teaches nanotechnology at Florida State University. Dr. Sharma's main research interest is in nanomaterial toxicity and microimag-ing and has 89 publications. He has received the highest awards by AACR, ISG and is the editor of three journals.

Yashpal Sharma is working as assistant professor in a Government Degree College in India. He has been awarded NIMS Internship fellowship 2011 to carry out research in the Biofunctional Materials Group, National Institute for Materials Science, Tsukuba, Japan. He is a recipient of the prestigious Young Scientist Award presented by International Association of Advanced Materials (I A AM). He has more than 15 research publications in national and international journals and conference proceedings. He is currently working in

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the area of biological applications of smart polymers and tissue engineering scaffolds.

Dominique Shum-Tim is a cardiac surgeon at McGill University Health Centre and an associate professor at Cardiothoracic Surgery research division. Over the past several years he has been work-ing on different cardiovascular research projects such as myocar-dial infarction and restenosis using stem cell and biomedical stents. Prior to this, Dr. Shum-Tim had been as a research fellow in Boston Children's Hospital working in collaboration with the Massachusetts Institute of Technology polymer scientists to create cardiovascular structures through tissue engineering principles.

Ashutosh Tiwari is an assistant professor of nanobioelectronics at Biosensors and Bioelectronics Centre, IFM-Linkoping University, Sweden as well as Editor-in-Chief of Advanced Materials Letters. He has published more than 125 articles and patents as well as author-ing/editing in the field of materials science and technology.

Bruno Therrien completed his undergraduate study at the University of Montreal, and obtained his PhD (1998) at the University of Berne under the supervision of Prof. Thomas Ward. He currently holds a position of associate professor at the University of Neuchatel, Switzerland. With more than 200 publications, his main research interests are supramolecular and bioorganometallic chemistry.

A. Tripathi is currently associated with Bhabha Atomic research Center, Mumbai, India. He received his PhD in biotechnology in 2011 and his research interests are in the area of advanced nano-biomaterials, stem cell research, regenerative medicine, tissue engi-neering, bioprocess engineering and environmental biotechnology. He received the prestigious postdoctoral K.S. Krishnan Award from the President of India. He conducted his postdoctoral research proj-ect collectively at Kyushu University, Japan and IIT-K. He has pub-lished 15 peer-reviewed articles and has one patent. He is also an executive board member of the 'Clini-india' Clinical Institute, India.

Aniket Wadajkar received his PhD in biomedical engineering from the University of Texas at Arlington in 2012. Currently, he is work-ing as research scientist at Applied DNA Sciences Incorporation, Stony Brook, NY. His research interests include biomaterials and

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nanoscopic drug carriers. Aniket has authored 18 journal papers and 2 book chapters. He is a recipient of predoctoral fellowship from American Heart Association; Alfred and Janet Potvin Outstanding Bioengineering Student award; and Who's Who Among American Universities and Colleges award.

Weitai Wu received a BS (2003) and a PhD (2008) from the University of Science and Technology of China. He is currently a full profes-sor of chemistry at Xiamen University, China. His research group is currently working in the smart biomaterials, energy and environ-mental materials, and supramolecular assembled nanomaterials.

Zhiwei Xie is a postdoctoral fellow at the Department of Bioengineering, the University of Texas at Arlington. He received his PhD degree in polymer engineering in 2010 from Auburn University. He has four peer-reviewed publications and an award of INTC Graduate Research Competition 2009. His research interests involve development of polymeric biomaterials and nanomaterials.

Soon Hong Yuk is a professor at College of Pharmacy, Korea University. He received his PhD from the Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) in 1987. He then joined the Department of Pharmaceutics and Pharmaceutical Chemistry at the University of Utah as a postdoc-toral fellow from 1987 to 1989. Also, he worked in Korea Research Institute of Chemical Technology (KRICT) to 1999 and Hannam University to 2010. His current research interest is nanomedicine for effective diagnosis and therapy.

Yang Zhao received a BE in materials from Harbin University of Science and Technology in 2008. He has been a PhD candidate in materials physics and chemistry at the Shanghai Institute of Ceramics, Chinese Academy of Sciences since 2009, working on the development of porous materials for biomedical applications.

Shuiqin Zhou is a professor of chemistry at College of Staten Island and Graduate Center, The City University of New York. Her research interest is focused on smart polymers and hybrid nano-materials for sensing, imaging, and drug delivery. She has over 90 peer-reviewed journal publications and book chapters.

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Yingchun Zhu is a professor of the Shanghai Institute of Ceramics, Chinese Academy of Sciences. Currently, his research areas include drug-delivery system, biosensors, and antibacterial biomaterials, published over 100 scientific papers which have been cited more than 2000 times by other scientists.

Rajesh Vasita obtained his PhD in bioengineering from the Indian Institute of Technology Kanpur, India. Currently he is working as a postdoctoral fellow at the University of Milan, Italy while also serv-ing as an assistant professor at the School of Life Sciences, Central University of Gujarat, India.

Fabrizio Gelain is the scientific vice-director of the Center for Nanomedicine and Tissue Engineering at Niguarda Ca' Granda Hospital in Milan and head of the Nanomedicine Unit at the "CSS-MENDEL" IRCCS Institute in Rome. He was awarded a PhD in bioengineering by the Polytechnic of Milan in 2005 and has worked at the MIT and at The Lawrence Berkeley National Lab.