Targeted Delivery of Small and Macromolecular Drugs

629 Pages·2010·16.36 MB·English

by  Ajit S. Narang

Targeted Delivery of
Small and
Macromolecular Drugs
Targeted Deliver y of
Small and
Macromolecular Drugs
Edited by
Ajit S. Narang | Ram I. Mahato
Boca Raton London New York
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Library of Congress Cataloging‑in‑Publication Data
Targeted delivery of small and macromolecular drugs / [edited by] Ram I. Mahato and Ajit S. Narang.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4200-8772-7 (alk. paper)
1. Drug targeting. I. Mahato, Ram I. II. Narang, Ajit S.
[DNLM: 1. Drug Delivery Systems. 2. Drug Administration Routes. 3. Drug Carriers. 4.
Macromolecular Substances--administration & dosage. 5. Molecular Weight. QV 785 T1845 2010]
RM301.63.T365 2010
615’.7--dc22 2010002143
Visit the Taylor & Francis Web site at
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and the CRC Press Web site at
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I dedicate this work to the sacrifices of my parents, Mr. Tirath Singh
and Mrs. Gurdip Kaur, and my wife, Swayamjot; to the love of my
brother, Supreet, and son, Manvir; and to the encouragement and
confidence bestowed on me by my teachers and mentors.
Ajit S. Narang
To my wife Subhashini, my children Kalika and Vivek for their love
and support, my mother for believing in me, and my students and
mentors who have always helped me in my quest for learning.
Ram I. Mahato
*****
The many benefits and potentials of
targeted drug delivery
is just one of the outcomes of
the entrepreneurial spirit of the innovators
and
our quest for
finding novel solutions to known challenges.
*****
Contents
Editors ...............................................................................................................................................xi
Contributors ...................................................................................................................................xiii
Chapter 1 Therapeutic Potential of Targeted Drug Delivery ........................................................1
Ajit S. Narang and Ram I. Mahato
PArT I Active Targeting
Chapter 2 Antibody Therapies for Liver Malignancy and Transplantation ................................13
John M. Luk and Kwong-Fai Wong
Chapter 3 Transferrin Receptor–Mediated Transcytosis in Intestinal Epithelial Cells
for Gastrointestinal Absorption of Protein Drugs ......................................................31
Nurmamet Amet, Xiaoying Chen, Hsin-Fang Lee,
Jennica Zaro, and Wei-Chiang Shen
Chapter 4 Ionizing Radiation for Tumor-Targeted Drug Delivery..............................................53
Roberto Diaz, Li Zhou, and Dennis E. Hallahan
PArT II Nucleic Acid Delivery and Targeting
Chapter 5 Recent Advances in Gene Expression and Delivery Systems ....................................83
Ravikiran Panakanti and Ram I. Mahato
Chapter 6 Cellular Barriers for Nucleic Acid Delivery and Targeting .....................................107
Arto Urtti
Chapter 7 Targeted Delivery Systems of Nonviral Nucleic Acid–Based Therapeutics ............115
Ga Yong Shim, Eun-Joong Kim, Rae Sung Chang,
Han Young Lee, and Yu-Kyoung Oh
Chapter 8 Delivery and Targeting of Oligonucleotides and siRNA .........................................147
Ningning Yang and Ram I. Mahato
Chapter 9 Liposomes for Nonviral Gene Delivery ...................................................................171
Jiasheng Tu, Yan Shen, Hui Pang, and Yubing Yu
vii
viii Contents
PArT III Intracellular/Organelle-Specific Strategies
Chapter 10 Delivering the Bullet to the Right Intracellular Target: A Cellular
Perspective on Drug Delivery ..................................................................................219
Maria Teresa Tarragó-Trani and Brian Storrie
Chapter 11 Mitochondria-Targeted Drug Delivery .....................................................................255
Volkmar Weissig and Gerard G. M. D’Souza
PArT IV Prodrug Strategies
Chapter 12 Site-Specific Prodrug Activation Strategies for Targeted Drug Action ...................277
Mark D. Erion
Chapter 13 Enzyme-Activated Prodrug Strategies for Targeted Drug Action ...........................311
Jarkko Rautio, Krista Laine, Lanyan Fang, Bing Han,
Kristiina Huttunen, and Duxin Sun
PArT V Organ- or Tissue-Specific Drug Delivery
Chapter 14 Targeting Colon and Kidney: Pathophysiological Determinants of
Design Strategy ........................................................................................................351
Ajit S. Narang and Ram I. Mahato
Chapter 15 Principles and Practice of Pulmonary Drug Delivery .............................................371
Vivek Gupta, Chandan Thomas, and Fakhrul Ahsan
Chapter 16 Recent Advances in Ocular Drug Delivery: Role of Transporters,
Receptors, and Nanocarriers ....................................................................................421
Gyan P. Mishra, Ripal Gaudana, Viral M. Tamboli, and Ashim K. Mitra
PArT VI Polymer–Drug Conjugates and Micelles
Chapter 17 Injectable Polymers for Regional Drug Delivery .....................................................457
Rajendra P. Pawar, Niteen R. Shinde, Narsinha M. Andurkar,
Satish A. Dake, and Abraham J. Domb
Contents ix
Chapter 18 Polymer–Drug Conjugates .......................................................................................481
Lucienne Juillerat-Jeanneret and Feride Cengelli
Chapter 19 Polymer Micelles for Drug Delivery ........................................................................513
Sungwon Kim and Kinam Park
PArT VII Stimuli-responsive Systems
Chapter 20 Multifunctional Stimuli–Responsive Nanoparticles for Targeted Delivery of
Small and Macromolecular Therapeutics ................................................................555
Srinivas Ganta, Arun Iyer, and Mansoor Amiji
Chapter 21 Physiological Stress Responsive Gene Regulation Systems for
Tissue Targeting ......................................................................................................587
Hyun Ah Kim and Minhyung Lee
Index ..............................................................................................................................................605
Editors
Ajit S. Narang works for the Bristol-Myers Squibb, Co. in New Brunswick, New Jersey, in the
biopharmaceutical aspects of drug delivery. He has over eight years of experience in the pharma-
ceutical industry in the development of oral dosage forms and drug delivery platforms. In addition
to the Bristol-Myers Squibb, Co., he has worked for Ranbaxy Research Labs (currently a subsidiary
of Daiichi Sankyo, Japan) in Gurgaon, India, and Morton Grove Pharmaceuticals (currently a sub-
sidiary of Wockhardt USA LLC, Parsippany, New Jersey) in Vernon Hills, Illinois. He graduated
from the University of Delhi in India and completed his postgraduate studies at the Banaras Hindu
University in India and at the University of Tennessee Health Science Center, Memphis. His current
research interests include innovations in drug product development and drug delivery technologies
that enable the pharmaceutical development of challenging molecules to resolve stability, pharma-
cokinetic, and pharmacodynamic issues. He has more than 35 publications and 3 pending patent
applications, and has contributed to the development of several marketed drug products.
Ram I. Mahato is a full-time professor in the Department of Pharmaceutical Sciences at the
University of Health Science Center, Memphis, Tennessee. He was a research assistant professor
at the University of Utah, Salt Lake City; a senior scientist at GeneMedicine, Inc., The Woodland,
Texas; and a postdoctoral fellow at the University of Southern California in Los Angeles,
Washington University in St. Louis, and Kyoto University, Japan. He received his BS in pharma-
ceutics from China Pharmaceutical University, Nanjin in 1989 and his PhD in pharmaceutics and
drug delivery from the University of Strathclyde, Glasgow in 1992. He is an author or coauthor of
79 peer-reviewed articles and book chapters, and has edited/written three books. He is also a special
features editor of Pharmaceutical Research and serves on the editorial boards of the Journal of
Drug Targeting, Expert Opinion on Drug Delivery, and Transplantation and Risk Management. His
research includes delivery and targeting of small molecules, oligonucleotides, siRNA, and genes.
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