NANOTECHNOLOGY IN HEALTH CARE

NANOTECHNOLOGY IN HEALTH CARE

NANOTECHNOLOGY IN HEALTH CARE Sanjeeb K. Sahoo

Published by Pan Stanford Publishing Pte. Ltd. Penthouse Level, Suntec Tower 3 8 Temasek Boulevard Singapore 038988 Email: editorial@panstanford.com Web: www.panstanford.com British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Nanotechnology in Health Care Copyright 2012 Pan Stanford Publishing Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. ISBN 978-981-4267-21-2 (Hardcover) ISBN 978-981-4267-35-9 (ebook) Printed in the USA

Contents Preface xi 1. Nanomedicine: Emerging Field of Nanotechnology to Human Health 1 Chandana Mohanty, Mallaredy Vandana, Abhalaxmi Singh, and Sanjeeb K. Sahoo 1.1 Introduction 1 1.2 Nanotechnology Approach to Nanomedicine 3 1.3 Application of Nanotechnology and Its Impact on Human Health/Nanomedicine 4 1.3.1 Pharmaceutical and Therapeutics 5 1.3.1.1 Drug delivery 5 1.3.1.2 Gene delivery 8 1.3.1.3 Vaccine delivery 11 1.3.2 Molecular Imaging and Diagnostic Tools 12 1.3.2.1 Molecular imaging 12 1.3.2.2 Diagnostic tools 16 1.3.3 Tissue Engineering 19 1.3.4 Stem Cell Research 23 1.3.5 Implant and Prosthesis in Nanomedicine 25 1.3.5.1 Assembly fabrication of implantable and prosthetic devices 25 1.3.5.2 Biological applications 27 1.3.5.3 Implant coatings 27 1.3.5.4 Implantable medical devices 28 1.4 Risks of Nanotechnology in Human Health Care 30 1.5 Future Prospective of Nanotechnology in Human Health Care 32 1.6 Conclusion 33

vi Contents 2. Nanomedicines Impacts in Ocular Delivery and Targeting 43 Yadollah Omidi, Jaleh Barar, and Hossein Hamzeiy 2.1 Introduction 43 2.2 Topical Absorption of Ocular Drug 46 2.3 Ocular Membranes, Barriers, and Transporters 47 2.3.1 Tear Film 48 2.3.2 Cornea and Corneal Route 49 2.3.3 Corneal Epithelium and Endothelium 50 2.3.4 Noncorneal Route, Conjunctiva, and Sclera 52 2.3.5 Iris, Ciliary Body, and Aqueous Humor Flow 54 2.3.6 Vitreous Body and Fluid Flow 54 2.3.7 Blood Aqueous Barrier 55 2.3.8 Retina and Blood Retinal Barrier 56 2.3.9 Ocular Transport Machineries 57 2.4 In vivo and in vitro Models 61 2.5 Ocular Pharmacotherapy 63 2.5.1 Conventional Pharmaceuticals 63 2.5.2 Emergence of Novel Technologies 65 2.5.3 Ocular Implants 67 2.5.4 Drug-Polymer Nanoformulations 68 2.5.5 Liposomal Nanomedicines 72 2.5.6 Nanostructured Dendrimers 74 2.6 Nanomedicines Paradigms in Ocular Diseases 76 2.6.1 Nanosuspensions in Ocular Inflammation 78 2.6.2 Photodynamic Therapy: Implementation of Nanosystems 82 2.6.3 Genonanomedicines, Monoclonal Antibodies, and Nanobodies 83 2.7 Bioavailability of Ocular Nanomedicines 85 2.8 Future Prospective of Ocular Therapies 87 3. Immunonanosystems to CNS Pathologies: State of the Art 107 G. Tosi, B. Ruozi, L. Badiali, L. Bondioli, D. Belletti, F. Forni, and M. A. Vandelli 3.1 Introduction 107

Contents vii 3.1.1 BBB Features 109 3.1.2 BBB Strategies for Drug Delivery 111 3.2 Nanoparticulate Systems: Brain Disease Nanomedicine and Nanotoxicology 112 3.2.1 Polymeric NPs 113 3.2.1.1 Polymers 113 3.2.1.2 NP fate 115 3.2.2 SLNPs 118 3.2.3 LPs 120 3.3 Rationale of the Ligand-Based Approach 123 3.3.1 Natural Substrates and Targeting Moieties as Ligands 123 3.3.2 Ligand-Based Approach and Immunonanosystems 127 3.4 Abs Used in Brain Targeting 130 3.4.1 TfR 130 3.4.1.1 OX26 Ab to TfR 131 3.4.1.2 8D3 MAb and R17-217 to TfR 132 3.4.2 Insulin 132 3.4.2.1 83-14 MAb to HINS-R 133 3.4.3 Folic Acid 134 3.5 Immuno-NPs 135 3.5.1 TfR Abs (OX26, R17-217) as Ligands 135 3.5.2 INS-R Abs (83-14 MAb) as Ligands 136 3.6 Immuno-SLNPs 137 3.6.1 TfR Ab (OX26) as Ligand 137 3.7.1 TfR Abs (OX26 and 8-D3) as Ligands 139 3.7.2 INS-R Ab (83-14 MAb) as Ligand 142 3.7.3 Coupled Ab Technology: 8D3 MAb (to TfR) and 83-14 MAb (to HIR) 144 3.7.4 Others 145 4. Pegylated Zinc Protoporphyrin: A Micelle-Forming Polymeric Drug for Cancer Therapy 169 Jun Fang, Hideaki Nakamura, Takahiro Seki, Haibo Qin, G. Y. Bharate, and Hiroshi Maeda 4.1 Introduction 169

viii Contents 4.2 Tumor-Targeted Oxidation Therapy Based on the EPR Effect 171 4.3 PEG-Zinc Protoporphyrin (PZP): A Micellar Form of HO-1 Inhibitor with Potential Anticancer Activity 172 4.3.1 HO-1 (HSP32) as an Anticancer Target and Use of Zinc Protoporphyrin 172 4.3.2 Synthesis and Physiochemical Characteristics of PZP 174 4.3.2.1 Synthesis and micelle formation of PZP 174 4.3.2.2 Spectroscopy of PZP 176 4.3.2.3 Stability of PZP micelles 177 4.3.2.4 Inhibitory activity of PZP against HO-1 179 4.3.3 Biological Characteristics of PZP 179 4.3.3.1 Tumor cell selective cytotoxicity 179 4.3.3.2 In vivo pharmacokinetics, tumor uptake, and tissue delivery of PZP 180 4.3.3.3 Antitumor effect of PZP 184 4.3.4 Mechanisms Involved in the Antitumor Effect of PZP 184 4.3.4.1 Induction of apoptosis through inhibition of HO-1 activity 184 4.3.4.2 New insight into the antitumor mechanisms of PZP involving oncogene 185 4.3.5 PDT: An Enhanced and Unique Antitumor Strategy of PZP 187 4.4 Cautions in PZP-Mediated Oxidation Therapy 190 4.5 Conclusion 191 5. ORMOSIL Nanoparticles: Nanomedicine Approach for Drug/Gene Delivery to the Brain 201 Indrajit Roy 5.1 Nanotechnology in Medicine 202 5.2 Brain 202 5.3 BBB Permeability of Nanoparticles 203 5.4 Gene Therapy in the Brain 203 5.5 Silica Nanoparticles 204 5.6 ORMOSIL Nanoparticles for Gene Delivery in the Brain 206 5.7 Future Perspectives 208

Contents ix 6. Magnetic Nanoparticles: A Versatile System for Therapeutics and Imaging 215 Fahima Dilnawaz, Abhalaxmi Singh, and Sanjeeb K. Sahoo 6.1 Introduction 215 6.2 Role of Superparamagnetic Nanoparticles in Therapeutics and Imaging 218 6.3 Functionalization of the Superparamagnetic Nanoparticles 219 6.3.1 Surface Functionalized Superparamagnetic Nanoparticles for MRI 220 6.4 Multimodal-Imaging Approach 222 6.4.1 Superparamagnetic-Based Multimodal- Imaging Probes 223 6.5 Superparamagnetic Nanoparticles for Synchronized MRI and Therapeutic Drug Delivery 226 6.5.1 Superparamagnetic Nanoparticles for MRI and Gene Delivery 228 6.5.2 Multifunctional Superparamagnetic Hybrid Nanosystem for Cancer Imaging and Therapy 230 6.6 Conclusions and Future Perspective 231 7. Nanobiotechnology: A New Generation of Biomedicine Innovative Nanotechnology in Key Areas of Biomedical Engineering and Cancer Therapy 237 Prasanna Vidyasekar, Pavithra Shyamsunder, and Rama S. Verma 7.1 Introduction 238 7.1.1 A New Tool 238 7.1.2 The New Tool in Medicine 240 7.2 Nanotechnology Rejuvenates Regenerative Medicine 241 7.2.1 Biomaterial Surfaces and Nano-scale Features 244 7.2.2 Surface Patterning: Creating Nano-scale Features on Growth Surfaces 244 7.2.3 Nanocoatings and Nanophase Materials 251 7.2.4 Materials for Nanoparticles 251 7.2.5 Nanofiber Scaffolds 253 7.2.6 Nanodevices 256

x Contents 7.3 Nanotechnology in Cancer Therapy 258 7.3.1 Characteristics of Typical Nanoparticles 259 7.3.2 Nanocarriers are Nanoparticles Used as Drug Delivery Systems 260 7.4 Conclusion 268 8 Aptamers and Nanomedicine 275 Sarah Shigdar, Adam Smith, and Wei Duan 8.1 SELEX: Methodology and Variations 276 8.1.1 Methodology 276 8.1.2 Variation of SELEX 278 8.2 Applications of Aptamers in Diagnostics 280 8.3 The Use of Aptamers as Therapeutic Agents 283 8.4 Targeted Drug Delivery 287 8.5 The Role of Aptamers in Molecular Imaging 290 9 Nanotechnology for Regenerative Medicine 297 Manasi Das, Chandana Mohanty, and Sanjeeb K. Sahoo 9.1 Introduction 297 9.2 Regenerative Medicine 298 9.3 Components of Regenerative Medicine 300 9.3.1 Cell Source 300 9.3.2 Biomaterials 301 9.3.3 Bioreactors 302 9.4 Nanotechnology for Regenerative Medicine Applications 303 9.4.1 Bone Regeneration 305 9.4.2 Skin Regeneration 306 9.4.3 Cardiac Tissue Regeneration 308 9.4.4 Vascular Tissue Engineering 309 9.4.5 Bladder Tissue Engineering 311 9.4.6 Neural Tissue Engineering 312 9.5 Conclusions 314 Index 321

Preface The newly recognized research thrust on nanomedicine, that is, the application of nanotechnology in human health care, is expected to have a revolutionary impact on the future of health care. To advance nanotechnology research for cancer prevention, diagnosis, and treatment, many countries have established alliances for nanotechnology in cancer for example, United States National Cancer Institute (NCI). Several approaches have been exploited for the development of nanotechnology for cancer molecular medicine. Nanoparticles offer some unique advantages as drug delivery and image enhancement agents. Different varieties of nanoparticulate systems are available, including nanoparticles, micelles, dendrimers, liposomes nanoassemblies, and polymer conjugates, which not only serve as a better platform for drug delivery to tumor sites but have also emerged as an advantageous regime over conventional chemotherapy. This book focuses on various nanotechnological strategies which show great promise for imaging and treatment of cancer by targeted delivery of drugs to tumor sites and alleviation of the side effects of chemotherapeutic agents. Multifunctional nanosystems also offer the opportunity for combining more than one drug or drug with imaging agents for wide-spectrum application. Contributions from world-renowned authorities proficient in their subjects are brought together here to provide a comprehensive treatise on the subject. The intended audience includes researchers active in nanoscience and technology in industry and academia, medical professionals, government officials responsible for research, and industrialists in pharmaceutical and biomedical technology. I hereby express my gratitude to all of the contributing authors for helping me successfully transmute the concept of the book into reality. Sanjeeb K. Sahoo June 2012