Drug Targeting: Organ-Specific Strategies, Volume 12 PDF
Preview Drug Targeting: Organ-Specific Strategies, Volume 12
Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Drug Targeting Organ-Specific Strategies Edited by Grietje Molema and Dirk K.F.Meijer Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Methods and Principles in Medicinal Chemistry Edited by R. Mannhold H. Kubinyi H.Timmerman Editorial Board G. Folkers, H.-D. Höltje, J.Vacca, H. van de Waterbeemd,T.Wieland Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Drug Targeting Organ-Specific Strategies Edited by Grietje Molema and Dirk K. F. Meijer Weinheim · New York · Chichester · Brisbane · Singapore ·Toronto Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Series Editors: Prof. Dr. Raimund Mannhold Prof. Dr. Hugo Kubinyi Prof. Dr. Hendrik Timmerman Biomedical Research Center BASF AG Ludwigshafen Faculty of Chemistry Molecular Drug Research Group c/o Donnersbergstrasse 9 Dept. of Pharmacochemistry Heinrich-Heine-Universität D-67256 Weisenheim am Sand Free University of Amsterdam Universitätsstraße 1 Germany De Boelelaan 1083 D-40225 Düsseldorf NL-1081 HV Amsterdam Germany The Netherlands Volume Editors: Dr. Grietje Molema Prof. Dr. Dirk K. F. Meijer University Centre for Pharmacy University Centre for Pharmacy Department of Pharmacokinetics Department of Pharmacokinetics and Drug Delivery and Drug Delivery Antonius Deusinglaan 1 Antonius Deusinglaan 1 NL-9713 AV Groningen NL-9713 AV Groningen The Netherlands The Netherlands This book was carefully produced. Nevertheless, authors, editors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No. applied for. British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library. Die Deutsche Bibliothek – CIP Cataloguing-in-Publication-Data A catalogue record for this publication is available from Die Deutsche Bibliothek ISBN 3-527-29989-0 © WILEY-VCH Verlag GmbH, D-69469 Weinheim (Federal Republic of Germany), 2001 Printed on acid-free paper. All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Composition: Datascan GmbH, D-64295 Darmstadt Printing: betz-druck GmbH, D-63291 Darmstadt Bookbinding: Wilhelm Osswald & Co., D-67433 Neustadt (Weinstraße) Printed in the Federal Republik of Germany. Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Preface It is our prime intention to cover the topics of this series as comprehensively as possible. Thus,we are very pleased to introduce this volume focussing on organ specific strategies of drug targeting. About hundred years ago Paul Ehrlich put forward his theory of “the magic bullet”as an approach to tame disease.Scientists have ever since worked on the principle of drug target- ing based on this idea of specifically delivering drugs to diseased cells.Especially nowadays that by high-throughput screening and molecular modelling techniques highly potent drugs are being developed that interfere with general (signal transduction) processes in cells in the body,the need for their application by a drug targeting approach has almost become in- evitable. Progress in the field of drug targeting has been slow till thirty years ago.With the advent of the monoclonal antibody technology in the mid seventies of the last century as well as the development of liposomal devices as carriers did the drug targeting field expand and did the clinical application become a feasible aim. Monoclonal antibodies,liposomes,polymers,proteins,and many other entities have ever since seen the light as carrier molecules.And,as with most technological developments,they have all encountered a vast array of difficulties,ranging from problems in the synthesis of the carriers and drug conjugates to unfavorable pharmacokinetics and toxicity. Furthermore, lack of knowledge on the anatomical and physiological barriers in the body hampered appli- cation.However,many problems have been solved,not in the least due to the advent of re- combinant DNA technology to construct better defined carriers that can be produced in large amounts,and advanced pharmaceutical formulation technology.Similarly,the rapid de- velopments in molecular biology,cell biology and immunology led to a better understanding of the processes taking place in vivoupon administration of carriers and conjugates.Impor- tant conclusion is that drug targeting has become a multidisciplinary research area. What has been achieved until now? In the year 2001,several liposome and antibody based strategies have been or will soon be approved for clinical application,some for the treatment of cancer,some for the treatment of bacterial infections,some for chronic inflammatory dis- eases.Furthermore many monoclonal antibodies without a drug or pharmacologically active molecule attached are in the clinic.Their intrinsic targeting and effector function is obvious- ly sufficient for the pharmacological effect. Only a few polymer or protein based drug targeting strategies have reached the clinic and an important question in the coming years will be whether these strategies eventually will reach it.All will depend on their effectiveness and improved toxicity profiles as compared to free drug only and the ease of their production at large scale. The present volume is in several respects unique.It provides a map of the body from the viewpoint of drug targeting/drug delivery.Potentials and limitations of targeting strategies VI Preface are discussed in the light of organ related diseases for each organ separately.Furthermore, novel technologies are described that may be useful in the future to allow an even better product to be developed that can be clinically exploited at a more rapid pace. The series editors are grateful to the contributors to this volume, in particular Grietje Molema and Dirk K.F.Meijer,as well as Wiley-VCH publishers,for the fruitful collaboration and the straightforward realization of this project. January 2001 Raimund Mannhold, Düsseldorf Hugo Kubinyi,Ludwigshafen Henk Timmerman,Amsterdam Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Foreword It was in the mid-1970s I think,just a few years after Brenda Ryman and I introduced lipo- somes as a drug delivery system,when a well meaning colleague af mine advised me not to put all my eggs in one basket.The eggs were liposomes and the basket my career.At the same time there were all sorts of prophecies and rumours from a variety of quarters about liposo- mal stability problems,expense,toxicity,difficulties with large scale manufacture,etc.Some went as far as to dismiss the system as a flash in the pan phenomenon.Indeed,the yellow brick road to the magic bullet is littered with systems that once made the headlines and then fell by the wayside.So,such comments on liposomes,and later on on antibodies,were not sur- prising.I believe that what made many of us persevere throughout the decades in developing drug carrier systems such as liposomes,and associated technologies was the realization that, for the foreseeable future at least,molecular modelling is not the answer to drug selectivity for most therapeutics.The vagaries of the biological milieu in vivoensures that optimal drug action (seen in the test tube) is compromised by such factors as opsonins and proteolytic en- zymes in the bloodstream,membrane barriers,loss through the kidneys,and premature in- terception of therapeutics by the reticuloendothelial system.In the case of liposomes,mono- clonal antibodies and some polymers,carrier development was greatly facilitated by their structural versatility which enabled the design of advanced versions of unique sophistication. The first generation of liposome-based systems approved for clinical use are believed to function on the basis of their passive uptake by the target tissues (e.g.the AmBisome and the virosome vaccine Hepaxal) or by avoiding certain tissues (e.g.heart,kidneys) that are prone to damage by the drug when given as such (e.g.Doxil,Daunoxome).The next challenge is to create or build on the systems that can be actively targeted to specific tissues or circulation cells for which systems such as liposomes have little or no affinity.They include a variety of molecules with genuine targeting properties,for instance (neo-) glycoproteins,monoclonal antibodies and fragments thereof,applied either as a means to deliver drugs attached to these biopolymers,or as homing devices when attached to the surface of other drug delivery sys- tems,for instance liposomes and other particle-type carriers.Success to that end will greatly enlarge the spectrum of therapeutics that can be selectively delivered,and widen the range of applications. In this respect,Grietje Molema,Dirk K.F.Meijer and a team of drug delivery experts have taken an important step with the present book.Unlike previous volumes,this one is not de- voted exclusively to liposome or antibody technologies.Rather,the book deals with organ- specific drug targeting strategies developed for the treatment of a wide spectrum of diseases and includes a collection of novel techniques applied to drug targeting research.Thus,the book provides a blueprint for both the experienced and the semi-experienced reader inter- ested in drug targeting and related optimization strategies. London,2001 Gregory Gregoriadis Drug Targeting Organ-Specific Strategies.Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) List of Contributors Jan-Willem Arends Ulrich Bickel Maastricht University Texas Tech University HSC Department of Pathology School of Pharmacy PO Box 616 Pharmaceutical Sciences 6200 MD Maastricht 1300 S Coulter the Netherlands Amarillo,Texas 79106 USA [email protected] Sigridur A.Ásgeirsdóttir Groningen University Institute for Drug Anne H.de Boer Exploration (GUIDE) Department of Pharmacokinetics and Drug Groningen University Institute for Drug Delivery Exploration (GUIDE) Ant.Deusinglaan 1 Department of Pharmaceutical Technology 9713 AV Groningen and Biopharmacy the Netherlands Ant.Deusinglaan 1 [email protected] 9713 AV Groningen the Netherlands [email protected] Leonie Beljaars Groningen University Institute for Drug Maaike Everts Exploration (GUIDE) Department of Pharmacokinetics and Drug Groningen University Institute for Drug Delivery Exploration (GUIDE) Ant.Deusinglaan 1 Department of Pharmacokinetics and Drug 9713 AV Groningen Delivery the Netherlands Ant.Deusinglaan 1 [email protected] 9713 AV Groningen the Netherlands [email protected] X List of Contributors Henderik W.Frijlink R.Folgert G.Haverdings Groningen University Institute for Drug Groningen University Institute for Drug Exploration (GUIDE) Exploration (GUIDE) Department of Pharmaceutical Technology Department of Pharmacokinetics and Drug and Biopharmacy Delivery Ant.Deusinglaan 1 Ant.Deusinglaan 1 9713 AV Groningen 9713 AV Groningen the Netherlands the Netherlands [email protected] [email protected] Arjan W.Griffioen Wijnand Helfrich Maastricht University/ Groningen University Institute for Drug University Hospital Maastricht Exploration (GUIDE) Department of Internal Medicine Department of Pathology and Laboratory Tumor Angiogenesis Laboratory Medicine Peter Debyelaan 25 Medical Biology Section 6202 AZ Maastricht Tumor Immunology Laboratory the Netherlands Hanzeplein 1 [email protected] 9713 GZ Groningen the Netherlands [email protected] Geny M.M.Groothuis Groningen University Institute for Drug Hennie R.Hoogenboom Exploration (GUIDE) Department of Pharmacokinetics and Drug Dyax bv Delivery PO Box 5800 Ant.Deusinglaan 1 6202 AZ Maastricht 9713 AV Groningen the Netherlands the Netherlands [email protected] [email protected] Jörg Huwyler Marijke Haas F.Hoffmann-LaRoche Ltd. Groningen University Institute for Drug CNS Research Exploration (GUIDE) PRBN,Bldg.68/323a Department of Clinical Pharmacology CH-4070 Basel Ant.Deusinglaan 1 Switzerland 9713 AV Groningen [email protected] the Netherlands [email protected] List of Contributors XI Young-Sook Kang Lou F.M.H.de Leij Physiology and Pathophysiology Laboratory Groningen University Institute for Drug College of Pharmacy Exploration (GUIDE) Sookmyung Women’s University Department of Pathology and Laboratory Chungpa-dong 2 ga 53-12 Medicine Yongsan gu,140-742 Medical Biology Section Seoul Tumor Immunology Laboratory Korea Hanzeplein 1 [email protected] 9713 GZ Groningen the Netherlands [email protected] Yukio Kato University of Tokyo Claudia S.Leopold Graduate School of Pharmaceutical Sciences University of Leipzig 7-3-1 Hongo Department of Pharmaceutical Technology Bunkyo-ku Schönauer Str.160 Tokyo 113-0033 04207 Leipzig [email protected] Germany [email protected] Robbert J.Kok Dirk K.F.Meijer Groningen University Institute for Drug Exploration (GUIDE) Groningen University Institute for Drug Department of Pharmacokinetics and Drug Exploration (GUIDE) Delivery Department of Pharmacokinetics and Drug Ant.Deusinglaan 1 Delivery 9713 AV Groningen Ant.Deusinglaan 1 the Netherlands 9713 AV Groningen [email protected] the Netherlands [email protected] Jos G.W.Kosterink Barbro N.Melgert University Hospital Groningen Department of Hospital and Clinical Groningen University Institute for Drug Pharmacy Exploration (GUIDE) Hanzeplein 1 Department of Pharmacokinetics and Drug 9713 GZ Groningen Delivery the Netherlands Ant.Deusinglaan 1 [email protected] 9713 AV Groningen the Netherlands [email protected]
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