BIOMATERIALS for DELIVERY and TARGETING of PROTEINS and NUCLEIC ACIDS � 2005 by CRC Press CRC PR ESS Boca Raton London New York Washington, D.C. BIOMATERIALS for DELIVERY and TARGETING of PROTEINS and NUCLEIC ACIDS EDITED BY Ram I. Mahato � 2005 by CRC Press This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. All rights reserved. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. Visit the CRC Press Web site at www.crcpress.com � 2005 by CRC Press No claim to original U.S. Government works International Standard Book Number 0-8493-2334-7 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper Library of Congress Cataloging-in-Publication Data Biomaterials for delivery and targeting of protiens and nucleic acids / edited by Ram I. Mahato. Includes bibliographical references and index. ISBN 0-8493-2334-7 (alk. paper) 1. Polymeric drug delivery systems. 2. Peptide drugs—Dosage forms. 3. Nucleic acids—Therapeutic use. I. Mahato, Ram I. RS201.P65B54 2005 6150.7–dc22 2004055434 � 2005 by CRC Press Dedication I dedicate this book to Vivek, Kalika, and my wife Subhashini for all their love and support; and to my students and mentors who have always helped me in my quest for learning and in achieving higher goals. � 2005 by CRC Press Preface Progress in biotechnology has created many opportunities for the development of protein- and nucleic acid-based therapeutics for the treatment of genetic and acquired diseases. There are numerous advanced books on polymer synthesis, drug delivery, oligonucleotides, and gene therapy, but there is an urgent need for a textbook for newcomers to this field including graduate students and young scientists, who have little understanding of the field. This book is expected to serve as a textbook and/or reference text for graduate courses in biomaterials and delivery of proteins and nucleic acids. Among scientists with different expertise, effective protein and nucleic acid- based therapeutics require a multi-disciplinary approach, such as molecular and cell biology, biochemistry, biophysics, polymer chemistry, colloid science, pharmaceutics, and medicine. Significant progress has been made in the use of biomaterials and polymeric carriers for the delivery of proteins, peptides, and nucleic acids (including plasmid DNA, antisense and antigene oligonucleo- tides, and siRNA). In addition to their use as carriers, polymers are finding increased use in polymer therapeutics, whereby the conjugated polymeric carriers usefully alter the properties of the protein or the nucleic acid. Liposomes have also been proven useful for delivery of proteins and nucleic acids. With this end in mind, I have organized this book to reflect various aspects of the field namely: � Use of polymers —structure, properties, synthesis and characterization � Crosslinking and PEGylation of proteins � Biocompatibility and biological barriers � In vivo and subcellular fate � Stability and formulation aspects of proteins and nucleic acids � Micro- and nano-particulate and liposomal delivery systems � Drug resistance and transporters � Protein transduction domain peptides � Antisense and antigene approaches � Artificial nucleic acid chaperones � Basic elements of nonviral gene therapy This book is written by international experts and leaders in their respective fields of knowledge. We have attempted to convey both an introductory understanding as well as latest developments in the field so that this book will be useful for both novice students and practicing scientists. We hope that this book will stimulate deeper understanding and interest in this integrated field, from people with diverse expertise and backgrounds. � 2005 by CRC Press About the Editor Ram I. Mahato is an assistant professor of pharmaceutics and drug delivery at the Departments of Pharmaceutical Sciences and Biomedical Engineering, University of Tennessee, Memphis. Dr. Mahato has served as a research assistant professor at the University of Utah; senior scientist at Valentis, Inc. (formerly, GeneMedicine, Inc.); and as a postdoctoral fellow at the University of Southern California, Washington University, and Kyoto University. He received a Ph.D. in pharmaceutics and drug delivery from the University of Strathclyde (Glasgow, U.K.) in 1992, and B.S. in pharmaceutics from China Pharmaceutical University (Nanjing, China) in 1989. Dr. Mahato has published more than 60 papers and book chapters, obtained one U.S. patent, and edited theme issues on nucleic acid delivery for the Journal of Drug Targeting and the Advanced Drug Delivery Reviews. In July 1992, he edited a book entitled Pharmaceutical Perspectives of Nucleic Acid- Based Therapeutics. He is a member of the editorial boards of the Journal of Drug Targeting and Expert Opinions on Drug Delivery. He is a frequent reviewer for the National Institutes of Health and several international journals. Dr. Mahato’s present research interests include design of novel polymers, cationic lipids, and lipopolymers for nonviral delivery of oligonucleotides and genes, use of modified adenovirus for gene delivery to primary cells, pharmacokinetics and biodistribution of nucleic acids, and protein delivery. � 2005 by CRC Press Contributors Shikha P. Barman Zycos, Inc. Lexington, Massachusetts Jean-Pierre Benoıˆt INSERM U646 Faculty of Pharmacy University of Angers Angers, France Joon Sig Choi Department of Biochemistry Chungnam National University Daejeon, Korea Abraham J. Domb Department of Medicinal Chemistry and Natural Products School of Pharmacy, Faculty of Medicine Hebrew University of Jerusalem Jerusalem, Israel Dagmar Fischer University of Marburg Marburg, Germany Sven Frokjaer The Danish University of Pharmaceutical Sciences Copenhagen, Denmark Hamidreza Ghandehari University of Maryland School of Pharmacy Department of Pharmaceutical Sciences Baltimore, Maryland Mark Gumbleton Pharmaceutical Cell Biology Welsh School of Pharmacy Cardiff University Cardiff, Wales � 2005 by CRC Press Ramareddy V. Guntaka Department of Molecular Sciences University of Tennessee Health Science Center Memphis, Tennessee Mary Lynne Hedley Zycos, Inc. Lexington, Massachusetts Kenneth D. Hinds Centocor, Inc. Radnor, Pennsylvania Lars Hovgaard The Danish University of Pharmaceutical Sciences Copenhagen, Denmark Kang Moo Huh Department of Pharmaceutics and Biomedical Engineering Purdue University School of Pharmacy West Lafayette, Indiana Young Jin Kim Department of Polymer Science and Engineering Chungnam National University Daejeon, South Korea Sung Wan Kim Center for Controlled Chemical Delivery Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah Salt Lake City, Utah Dagmar Klein Diabetes Research Institute University of Miami School of Medicine Miami, Florida Minhyung Lee Clinical Research Center Department of Molecular Gene Medicine Inha University Medical School Inchon, Korea Sang Cheon Lee Department of Pharmaceutics and Biomedical Engineering Purdue University School of Pharmacy West Lafayette, Indiana � 2005 by CRC Press Zheng-Rong Lu Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah Salt Lake City, Utah Ram I. Mahato Department of Pharmaceutical Sciences University of Tennessee Health Science Center Memphis, Tennessee Atsushi Maruyama Institute of Materials Chemistry and Engineering Kyushu University Fukuoka, Japan Bernd Meibohm Department of Pharmaceutical Sciences University of Tennessee Health Science Center Memphis, Tennessee Tamara Minko Department of Pharmaceutics The State University of New Jersey Piscataway, New Jersey Anjan Nan University of Maryland School of Pharmacy Department of Pharmaceutical Sciences Baltimore, Maryland Yadollah Omidi Pharmaceutical Cell Biology Welsh School of Pharmacy Cardiff University Cardiff, Wales Tooru Ooya School of Materials of Science Japan Advanced Institute Science and Technology Ishikawa, Japan David Oupicky´ Department of Pharmaceutical Sciences Wayne State University Detroit, Michigan � 2005 by CRC Press Jong-Sang Park Department of Chemistry Seoul National University Seoul, Korea Kinam Park Department of Pharmaceutics and Biomedical Engineering Purdue University School of Pharmacy West Lafayette, Indiana Catherine Passirani INSERM U646 Faculty of Pharmacy University of Angers Angers, France Ricardo L. Pastori Diabetes Research Institute University of Miami School of Medicine Miami, Florida Rajendra P. Pawar Department of Medicinal Chemistry and Natural Products School of Pharmacy, Faculty of Medicine Hebrew University of Jerusalem Jerusalem, Israel Melina M. Ribeiro Diabetes Research Institute University of Miami School of Medicine Miami, Florida Camillo Ricordi Diabetes Research Institute University of Miami School of Medicine Miami, Florida Andreas Scha¨ tzlein Department of Medical Oncology Beatson Laboratories University of Glasgow Glasgow, Scotland Ikumi Tamai Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba, Japan � 2005 by CRC Press