NANOTECHNOLOGY IN HEALTH CARE

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3 NANOTECHNOLOGY IN HEALTH CARE

5 NANOTECHNOLOGY IN HEALTH CARE Sanjeeb K. Sahoo

6 Published by Pan Stanford Publishing Pte. Ltd. Penthouse Level, Suntec Tower 3 8 Temasek Boulevard Singapore editorial@panstanford.com Web: 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 (Hardcover) ISBN (ebook) Printed in the USA

7 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 Nanotechnology Approach to Nanomedicine Application of Nanotechnology and Its Impact on Human Health/Nanomedicine Pharmaceutical and Therapeutics Drug delivery Gene delivery Vaccine delivery Molecular Imaging and Diagnostic Tools Molecular imaging Diagnostic tools Tissue Engineering Stem Cell Research Implant and Prosthesis in Nanomedicine Assembly fabrication of implantable and prosthetic devices Biological applications Implant coatings Implantable medical devices Risks of Nanotechnology in Human Health Care Future Prospective of Nanotechnology in Human Health Care Conclusion 33

8 vi Contents 2. Nanomedicines Impacts in Ocular Delivery and Targeting 43 Yadollah Omidi, Jaleh Barar, and Hossein Hamzeiy 2.1 Introduction Topical Absorption of Ocular Drug Ocular Membranes, Barriers, and Transporters Tear Film Cornea and Corneal Route Corneal Epithelium and Endothelium Noncorneal Route, Conjunctiva, and Sclera Iris, Ciliary Body, and Aqueous Humor Flow Vitreous Body and Fluid Flow Blood Aqueous Barrier Retina and Blood Retinal Barrier Ocular Transport Machineries In vivo and in vitro Models Ocular Pharmacotherapy Conventional Pharmaceuticals Emergence of Novel Technologies Ocular Implants Drug-Polymer Nanoformulations Liposomal Nanomedicines Nanostructured Dendrimers Nanomedicines Paradigms in Ocular Diseases Nanosuspensions in Ocular Inflammation Photodynamic Therapy: Implementation of Nanosystems Genonanomedicines, Monoclonal Antibodies, and Nanobodies Bioavailability of Ocular Nanomedicines Future Prospective of Ocular Therapies 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

9 Contents vii BBB Features BBB Strategies for Drug Delivery Nanoparticulate Systems: Brain Disease Nanomedicine and Nanotoxicology Polymeric NPs Polymers NP fate SLNPs LPs Rationale of the Ligand-Based Approach Natural Substrates and Targeting Moieties as Ligands Ligand-Based Approach and Immunonanosystems Abs Used in Brain Targeting TfR OX26 Ab to TfR D3 MAb and R to TfR Insulin MAb to HINS-R Folic Acid Immuno-NPs TfR Abs (OX26, R17-217) as Ligands INS-R Abs (83-14 MAb) as Ligands Immuno-SLNPs TfR Ab (OX26) as Ligand TfR Abs (OX26 and 8-D3) as Ligands INS-R Ab (83-14 MAb) as Ligand Coupled Ab Technology: 8D3 MAb (to TfR) and MAb (to HIR) Others 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

10 viii Contents 4.2 Tumor-Targeted Oxidation Therapy Based on the EPR Effect PEG-Zinc Protoporphyrin (PZP): A Micellar Form of HO-1 Inhibitor with Potential Anticancer Activity HO-1 (HSP32) as an Anticancer Target and Use of Zinc Protoporphyrin Synthesis and Physiochemical Characteristics of PZP Synthesis and micelle formation of PZP Spectroscopy of PZP Stability of PZP micelles Inhibitory activity of PZP against HO Biological Characteristics of PZP Tumor cell selective cytotoxicity In vivo pharmacokinetics, tumor uptake, and tissue delivery of PZP Antitumor effect of PZP Mechanisms Involved in the Antitumor Effect of PZP Induction of apoptosis through inhibition of HO-1 activity New insight into the antitumor mechanisms of PZP involving oncogene PDT: An Enhanced and Unique Antitumor Strategy of PZP Cautions in PZP-Mediated Oxidation Therapy Conclusion ORMOSIL Nanoparticles: Nanomedicine Approach for Drug/Gene Delivery to the Brain 201 Indrajit Roy 5.1 Nanotechnology in Medicine Brain BBB Permeability of Nanoparticles Gene Therapy in the Brain Silica Nanoparticles ORMOSIL Nanoparticles for Gene Delivery in the Brain Future Perspectives 208

11 Contents ix 6. Magnetic Nanoparticles: A Versatile System for Therapeutics and Imaging 215 Fahima Dilnawaz, Abhalaxmi Singh, and Sanjeeb K. Sahoo 6.1 Introduction Role of Superparamagnetic Nanoparticles in Therapeutics and Imaging Functionalization of the Superparamagnetic Nanoparticles Surface Functionalized Superparamagnetic Nanoparticles for MRI Multimodal-Imaging Approach Superparamagnetic-Based Multimodal- Imaging Probes Superparamagnetic Nanoparticles for Synchronized MRI and Therapeutic Drug Delivery Superparamagnetic Nanoparticles for MRI and Gene Delivery Multifunctional Superparamagnetic Hybrid Nanosystem for Cancer Imaging and Therapy Conclusions and Future Perspective 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 A New Tool The New Tool in Medicine Nanotechnology Rejuvenates Regenerative Medicine Biomaterial Surfaces and Nano-scale Features Surface Patterning: Creating Nano-scale Features on Growth Surfaces Nanocoatings and Nanophase Materials Materials for Nanoparticles Nanofiber Scaffolds Nanodevices 256

12 x Contents 7.3 Nanotechnology in Cancer Therapy Characteristics of Typical Nanoparticles Nanocarriers are Nanoparticles Used as Drug Delivery Systems Conclusion Aptamers and Nanomedicine 275 Sarah Shigdar, Adam Smith, and Wei Duan 8.1 SELEX: Methodology and Variations Methodology Variation of SELEX Applications of Aptamers in Diagnostics The Use of Aptamers as Therapeutic Agents Targeted Drug Delivery The Role of Aptamers in Molecular Imaging Nanotechnology for Regenerative Medicine 297 Manasi Das, Chandana Mohanty, and Sanjeeb K. Sahoo 9.1 Introduction Regenerative Medicine Components of Regenerative Medicine Cell Source Biomaterials Bioreactors Nanotechnology for Regenerative Medicine Applications Bone Regeneration Skin Regeneration Cardiac Tissue Regeneration Vascular Tissue Engineering Bladder Tissue Engineering Neural Tissue Engineering Conclusions 314 Index 321

13 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

NANOTHERAPEUTICS. Drug Delivery Concepts in Nanoscience

NANOTHERAPEUTICS. Drug Delivery Concepts in Nanoscience NANOTHERAPEUTICS Drug Delivery Concepts in Nanoscience This page intentionally left blank NANOTHERAPEUTICS Drug Delivery Concepts in Nanoscience edited by Alf Lamprecht of France PAN STANFORD PUBLISHING