Targeting of Drugs 4: Advances in System Constructs PDF
Preview Targeting of Drugs 4: Advances in System Constructs
Targeting of Drugs 4 Advances in System Constructs NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics New York and London C Mathematical and Physical Sciences K1uwer Academic Publishers o Behavioral and Social Sciences Dordrecht, Boston, and London E Applied Sciences F Computer and Systems Sciences Springer-Verlag G Ecological Sciences Berlin, Heidelberg, New York, London, H Cell Biology Paris, Tokyo, Hong Kong, and Barcelona I Global Environmental Change Recent Volumes in this Series Volume 267 - Bioelectrochemistry IV: Nerve Muscle Function Bioelectrochemistry, Mechanisms, Bioenergetics, and Control edited by Bruno Andrea Melandri, Giulio Milazzo, and Martin Blank Volume 268 - Advances in Molecular Plant Nematology edited by F. Lamberti, C. De Giorgi, and David McK. Bird Volume 269 - Ascomycete Systematics: Problems and Perspectives in the Nineties edited by David L. Hawksworth Volume 270 - Standardization of Epidemiologic Studies of Host Susceptibility edited by Janice Dorman Volume 271 - Oscillatory Event-Related Brain Dynamics edited by Christo Pantev, Thomas Elbert, and Bernd LOtkenhoner Volume 272 - Photobiology in Medicine edited by Giulio Jori, Roy H. Pottier, Michael A. J. Rodgers, and T. G. Truscott Volume 273 - Targeting of Drugs 4: Advances in System Constructs edited by Gregory Gregoriadis, Brenda McCormack, and George Poste Series A: Life Sciences Targeting of Drugs 4 Advances in System Constructs Edited by Gregory G regoriadis and Brenda McCormack School of Pharmacy University of London London, England and George Poste SmithKline Beecham Pharmaceuticals King of Prussia, Pennsylvania Springer Science+B usiness Media, LLC Proceedings of a NATO Advanced Study Institute on Targeting of Drugs: Advances in System Constructs, held June 24-July 5, 1993, in Cape Sounion, Greece NATO-PCO-DATA BASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to more than 30,000 contributions from international scientists published in all sections of the NATO ASI Series. Access to the NATO-PCO-DATA BASE is possible in two ways: —via online FILE 128 (NATO-PCO-DATA BASE) hosted by ESRIN, Via Galileo Galilei, I-00044 Frascati, Italy —via CD-ROM "NATO Science and Technology Disk" with user-friendly retrieval software in English, French, and German (©WTV GmbH and DATAWARE Technologies, Inc. 1989). The CD-ROM also contains the AGARD Aerospace Database. The CD-ROM can be ordered through any member of the Board of Publishers or through NATO-PCO, Overijse, Belgium. Library of Congress Cataloging-in-Publication Data Targeting of drugs 4 : advances in system constructs / edited by Gregory Gregoriadis and Brenda McCormack and George Poste. p. cm. — (NATO ASI series. Series A, Life sciences ; v. 273) Proceedings tcf] a NATO Advanced Study Institute on Targeting of Drugs: Advances in System Constructs, held June 24-July 5, 1993, in Cape Sounion, Greece"—T.p. verso. Published in cooperation with NATO Scientific Affairs Division. Includes bibliographical references and index. 1. Drug targeting—Congresses. I. Gregoriadis, Gregory. II. McCormack, Brenda. III. Poste, George. IV. North Atlantic Treaty Organization. Scientific Affairs Division. V. NATO Advanced Study Institute on Targeting of Drugs- Advances in System Constructs (1993 : Akra Sounion, Greece) VI. Title. Targeting of drugs four. VII. Series. [DNLM. 1. Drug Carriers—congresses. 2. Drug Delivery Systems- -congresses. 3. Drugs—administration & dosage—congresses. QV 785 T185 1994] RS200.T37 1994 615' .7—dc20 DNLM/DLC for Library of Congress 94-41747 CIP ISBN 978-1-4899-1209-1 ISBN 978-1-4899-1207-7 (eBook) DOI 10.1007/978-1-4899-1207-7 © Springer Science+Business Media New York 1994 Originally published by Plenum Press, New York in 1994 Softcover reprint of the hardcover 1st edition 1991 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE The NATO Advanced Studies Institute series "Targeting of Drugs" was originated in 1981. It is now a major international forum, held every two years in Cape Sounion, Greece, in which the present and the future of this important area of research in drug delivery is discussed in great depth. Previous ASIs of the series dealt with drug carriers of natural and synthetic origin, their interaction with the biological milieu, ways by which the latter influences such interaction, strategies by which milieu interference curtailing the function of drug carriers is circumvented and, more recently, with the application of drug carriers for the delivery of peptides and proteins. The present book contains the proceedings of the 7th NATO ASI "Targeting of Drugs: Advances in System Constructs", held in Cape Sounion during 24 June - 5 July 1993. As the title implies, the book deals with a variety of approaches to carrier design or modification that contribute to optimal carrier function. We express our appreciation to Mrs Concha Perring for her assistance with the organization of the ASI. We thank Dr. G. Deliconstantinos who, as chairperson of the Local Committee, contributed to the success of the Institute. The ASI was held under the sponsorship of NATO Scientific Affairs Division and co-sponsored and generously financed by SmithKline Beecham Pharmaceuticals (King of Prussia). Financial assistance was also provided by Liposome Technology Inc. (Menlo Park), Vestar Inc. (San Dimas) and Zeneka (Macclesfield). Gregory Gregoriadis Brenda McCormack George Poste August 1994 v CONTENTS Drug targeting with glycoproteins and other peptide carriers: An overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 D.K.F. Meijer Sugar specific delivery of drugs, oligonucleotides and genes. . . . . . . . . . . . . . . . 31 M. Monsigny, A.-e. Roche, P. Midoux and R. Mayer The use of MSH derivatives for targeting to melanomas. . . . . . . . . . . . . . . . . . . 51 D.R. Bard, e.G. Knight, E.P. Wraight, J.Van Beeumen, B.Deveese and F. Jacquemotte The immunogenicity of recombinant proteins and of "magic bullets" represents the main obstacle for the effective in vivo targeting of biologic response modifiers (BRMs) . . . . . . . . . . . . . . . . . . . . . . . . . 59 A.H. Sehon Targeting of drugs to tumors: The use of the plasminogen activator inhibitor as a ligand. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 J. Jankun Advances in diagnosis and treatment of neoplasia using radioactive monoclonal antibodies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 A. Maraveyas and A.A. Epenetos Targeting transcription factors to inhibit selectively gene expression in particular cell types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 A.e. Allison and E.M. Eugui Design, biological properties and delivery of antisense oligonucleotides. . . . . . . . 101 J.S. Cohen Liposomes in vivo: Control of behaviour. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 G. Gregoriadis Passive targeting of anthracyclines entrapped in 10ng-circulating(Stealth) Iiposomes in the treatment of cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . 119 T.M. Allen Liposomal drug delivery: possibilities for manipulation. . . . . . . . . . . . . . . . . . . . 129 G. Storm, I.A.1.M. Bakker-Woudenberg, M.e. Woodle, G. Blume, U.K. Nassander, M.H. Vingerhoeds, H. Haisma, and D.1.A. Crommelin Polysialic acids: In vivo properties and possible uses in drug delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 B. McCormack and G. Gregoriadis vii Red blood cells as carriers of drugs against retroviruses. . . . . . . . . . . . . . . . . . 147 M. Magnani, L. Rossi, L. Chiarantini, A. Fraternale and A. Casabianca Nanoparticles for the delivery of pep tides and proteins. . . . . . . . . . . . . . . . . . . 153 P. Couvreur and F. Puisieux New poly(methylidene malonate 2.1.2) nanoparticles: Recent developments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 P. Breton, D. Roy, L. Marchal-Heussler, C. Seguin, P. Couvreur and F. Lescure Oral uptake and translocation of nanoparticles: A real but useful phenomenon? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 AT. Florence, A.M. Hillery, N. Hussain and P.U. Jani Particulate systems for site specific drug delivery. . . . . . . . . . . . . . . . . . . . . . . 183 S.S. Davis and L. mum Participant's Photograph. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 viii DRUG TARGETING WITH GLYCOPROTEINS AND OTHER PEPTIDE CARRIERS: AN OVERVIEW Dirk K.F. Meijer Dept of Pharmaceutical Pharmacology and Clinical Pharmacy, section Pharmacokinetics and Drug Delivery, Groningen Inst for Drug Studies, University Centre for Pharmacy, Ant. Deusinglaan 2, 9713 AW Groningen, The Netherlands INTRODUCTION Drug targeting is aimed at the manipulation of drug distribution in the whole body in order to increase the therapeutic efficiency and decrease side effects and toxicity. In vitro studies with potential target cells can be helpful to study the relative rates of endocytosis, carrier degradation and release of the targeted drug. However, studies in the intact organism, also in the diseased state, should provide more definite clues as to the cell specificity of the chosen carrier system, possible toxicity and immunogenicity of the carrier as well as the potential to pass anatomical barriers en route to the target cells (for some general guidelines in drug targeting research, Fig. 1). Currently available carrier systems include particle type of carriers such as liposomes, lipid particles (LDL, HDL) and nanoparticles. Soluble carrier systems are prepared from monoclonal antibodies, modified plasmaproteins, polyamino-acids, polysaccharides and other bio-degradable polymers (see Fig. 2). In some cases the peptide carrier can be designed such that it contributes to the therapeutic effects (Meijer et ai, 1992) The mechanisms responsible for the disposition of peptides in the body include carrier-mediated transport (liver, CNS), filtration and reabsorption (kidneys), as well as receptor mediated endocytosis and phagocytosis. Important features determining the fate in the body are amino-acid composition, protein conformation and folding, overall size, net charge, presence of sugars, aggregation state and potential opsonization by blood components. Small peptides (up to 12 amino-acids) can be efficiently cleared by the liver depending on hydrophobicity and charge through four different carrier-systems, some of which are bile acid transporters (see Fig. 3). Time and dose dependent kinetics, extremely short half-lives and low bioavailability can therefore result (Meijer and Ziegler, 1993). Larger peptides (up to 60 kD) are easily filtrated by the kidneys but often fully reabsorbed and degraded in renal Iysosomes. Such low molecular weight proteins (LMWP's) can be used as drug carriers for renal-specific drug delivery. Targeting to the kidney of anti-immflamatory drugs, antimicrobial agents, ACE inhibitors and dopaminergic compounds have been studied. a. It is preferable to test drug·delivery preparations as soon as possible In the whole body. b. It is advisable to test dug-delivery preparations with regard to possible immunogenicity in an early stage of development. c. Cell-specific distribution of the drug-targeting preparations as well as the rate of drug release from the carrier should be studied in vivo both in the normal and the pathological situation. d. Drug loading of the carrier should be carefully balanced: sufficient drug molecules should be internalized to obtain therapeutic levels however excessive loading may corrupt cell specificity of the carrier. e. A type of carrier should be chosen that IS relatively non-toxic also with regard to its degradation products. f. The chosen carrier should be able to pass anatomical barriers in the body en route to the target tissues. g. Since parental administration is required, drug targeting formulations should have major advantages compared with the parent drug. Fig. 1 General guidelines in drug delivery research. Larger (glyco-)proteins are often recognized by sugar specific receptors or scavenger receptors in various cell types in the body. This can occur directly or after opsonization with circulating plasma components. For instance the extent and type of glycosylation can be crucial for the elimination of monoclonal antibodies while complex formation with circulating antigens can largely determine the fate in the body (Fc receptors). Some Viral receptors sCD4; CD4-immunoadhesins; CD4-toxins (viral inf.) • Immunotoxins (tumors, rheumatic dis., viral inf.,graft v host reactions) • Liposomes (solid tumors, lymphomas/leukemias, dermal dis., fungal inf., bact.lviral inf., vaccination) Polymeric matrices (Iymphomaslleukemias, bact. i nfect. , solid tumors, brain tumors) • Monoclonal antibodies (tumor imaging, solid tumors, lymphomas/ leukemias, cardiovasc. dis, autoimmune dis.) • Transfected cells (tumors, HIV inf., genetic deficiences) Other potential carriers Glycoproteins, LMWPs, HDULDL, bispecifc ASs catalytic ASs, pegylated proteins, poly-amino acids(sugar deriv.), nanoparticles Fig. 2 Carrier modalities currently employed in drug delivery research for the treatment or prevention of disease. 2
The list of books you might like
