Table Of ContentLIPOSOMES as
TOOLS
in
BASIC RESEARCH
and
INDUSTRY
Edited by
Jean R. Philippot, Ph.D.
CNRS Research Director
Membrane Interactions Laboratory
University of Montpellier II
Montpellier, France
Francis Schuber, Ph.D.
CNRS Research Director
Bioorganic Chemistry Laboratory
Loius Pasteur University
Strasbourg-Illkirch, France
First published 1995 by CRC Press
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PREFACE
This book, devoted to a broader understanding of liposomes, is not aimed at people engaged in current
uses of these vesicles in fields such as drug delivery, targeting, and other pharmacological fields. The
liposome is a versatile tool which can be used in many domains, including basic research and applied
technology. We aim to present these different domains, and to describe some of the main results already
obtained. Most of the liposome applications which are already well documented in other books will be
excluded from this presentation, with the exception of some very recent developments.
Liposomes have been widely used to reconstitute membrane functions due to the similarity between
the liposome bilayer and biological membranes. However, recent progress (e.g., mild solubilization of
membranes) has completely changed our perspectives in this field. Liposomes are also increasingly used
in studies performed to understand such important phenomena as endocytosis, membrane fusion, antigen
processing, and T cell presentation.
Over the past few years new types of liposomes have appeared, e.g. made of nonphospholipid
molecules, which have opened new perspectives of applications because of their high resistance in body
fluids, their possibility of carrying oil, and their cheapness. These lipid vesicles already used in cosme
tology have begun to be manufactured for many other industrial and agricultural uses. On the other hand,
pH-sensitive liposomes, Stealth® liposomes, and cationic liposomes have enlarged and improved the
application field of liposomes in clinical research.
This book should cover these different uses of liposomes with particular attention to new formulations
and new applications. It will be of interest to people involved in the field of cellular biology and other
related biological disciplines, as well as those having to improve their knowledge on the different
possibilities of the liposome concept.
THE EDITORS
Jean R. Philippot, Ph.D., is a Research Director at the Centre National de la Recherche Scientifique
(CNRS), France and Director of the Membrane Interactions Laboratory (URA-CNRS 530) at the
University of Montpellier II. He received his graduate degree from the University of Sciences of
Montpellier in 1958 and obtained his Ph.D. degree at Paris-Sorbonne University in 1962. He is an
engineer in Organic Chemistry from the Ecole Nationale Supérieure de Chimie de Montpellier. In 1963
he was a postdoctoral fellow at the Physiological Department of Cambridge University, England.
In 1958, Dr. Philippot was appointed to the CNRS. He served as Visiting Scientist at the Pharmalogical
Laboratory of the Bern Veterinary School, Switzerland, from 1967 to 1968; as Professor of biophysics
at Montpellier Medical School, from 1968 to 1972; and as Visiting Professor in the Radiobiology
Department of Tufts Medical School in Boston, from 1974 to 1976.
Dr. Philippot is a founding member of the Groupe Thématique de Recherche sur les Vecteurs (GTRV),
the French Society for Drug Delivery. He also serves as a consultant for several French and American
pharmaceutical companies.
He has carried out research in such diverse fields as the active transport of ions in erythrocytes and
feedback regulation of cholesterol biosynthesis. Since 1980, he has worked, published, and lectured on
the targeting of drugs with liposomes and has written over 100 papers and book chapters, as well as co
editing one book on liposomes.
Francis Schuber, Ph.D., is a Research Director at the Centre National de la Recherche Scientifique
Department (CNRS) and is Head of the Bioorganic Chemistry Laboratory (associated with CNRS) at the
Pharmacy of the University Louis Pasteur in Strasbourg-Ilkirch, France.
Dr. Schuber graduated from the University of Strasbourg in 1963 with a B.S. in Chemistry. In 1967,
he obtained his Ph.D. in Chemistry from the same institution. He was a postdoctoral fellow in the
Chemistry Department of the University of Ottawa, Canada, from 1968 to 1970 and in 1973 was a
Visiting Professor at McGill University in Montreal, Canada. From 1981 to 1982, he stayed at the Cancer
Research Institute at the University of California, San Francisco.
Dr. Schuber was appointed to the CNRS in 1966 where he has spent most of his career. He is a member
of the American Chemical Society, the Société Française de Chimie, and the Société Française de
Biochimie et Biologie Moléculaire. In 1976, Dr. Schuber, along with Professor P. Couvreur, founded the
Groupe Thématique de Recherche sur les Vecteurs (GTRV), the French Society for Drug Delivery. He
also serves as a consultant for several pharmaceutical companies.
Dr. Schuber is the author or co-author of about 100 papers and book chapters and has co-edited one
book on liposomes. His current research interests relate to bioorganic chemistry: chemical enzymology,
bioconjugation chemistry, synthesis of ligands for targeting (liposomes, genes), and synthetic vaccines.
CONTRIBUTORS
Jean-Paul Behr, Ph.D. Christan Marechal, Ph.D.
Lab de Chimie Génétique LVMH Service Propriété Industrielle
CNRS URA 1386 Paris, France
Faculté de Pharmacie de Strasbourg
Illkirch, France Rajiv Mathur
Micro Vesicular System, Inc.
David Collins, Ph.D. Nashua, New Hampshire
Department of Pharmaceutics and
Drug Delivery Pierre G. Milhaud, Ph.D.
AMGEN Center Institut de Génétique Moléculaire
Thousand Oaks, California CNRS
Montpellier, France
Robert J. Debs, Ph.D.
Cancer Research Institute Roger R.C. New, Ph.D.
University of California Cortecs Research Laboratory
San Francisco, California London School of Pharmacy
London, England
Nejat Düzgüneç, PhD.
Department of Microbiology Shlomo Nir, Ph.D.
University of the Pacific The Seagram Centre
School of Dentistry Faculty of Agriculture
San Francisco, California Hebrew University of Jerusalem
Rehovot, Israel
Martin Friede, Ph.D.
Université Louis Pasteur Demetrios Papahadjopoulos, Ph.D.
CNRS URA 1386 University of California
Faculté de Pharmacie de Strasbourg Cancer Research Institute and
Strasbourg-Illkirch, France Department of Pharmacology
San Francisco, California
Alberto A. Gabizon, M.D., Ph.D.
Sharett Institute of Oncology Pierre Perrier, Ph.D.
Hadassah Medical Center Parfums Christian Dior
Jerusalem, Israel Saint Jean de Braye, France
Dick Hoekstra, Ph.D. Jean R. Philippot, Ph.D.
Department of Physiological Chemistry Université Monpellier II
University of Groningen Department Biologie-Santé
Groningen, The Netherlands CNRS URA 530
Montpellier, France
S. Kumar, Ph.D.
Vineland Laboratories Bruno Pitard, Ph.D.
Vineland, New Jersey Section de Bioénergétique
Centre d'Etudes Nucléaire de Saclay
Lee Leserman, M.D., Ph.D. Gif-sur-Yvette, France
Centre d*Immunologie
INSERM-CNRS de Marseille-Luminy Christophe O. Puyal
Marseille, France Université Montpellier II
Department Biologie-Santé
Maria C.P. de Lima, Ph.D. CNRS-URA 530
Department of Biochemistry Montpellier, France
Center for Neurosciences
and Cell Biology Gérard Redziniak, Ph.D.
University of Coimbra Parfums Christian Dior
Coimbra, Portugal Saint Jean de Braye, France
Jean-Serge Remy, Ph.D. Colin Tilcock, Ph.D.
Lab de Chimie Génétique Department of Radiology
CNRS URA 1386 University of British Columbia
Faculté de Pharmacie de Strasbourg Vancouver, Canada
Illkirch, France
Carole Varanelli
Micro Vesicular System, Inc.
Jean-Louis Rigaud, Ph.D.
Nashua, New Hampshire
Section de Bioénergéteque
Centre d*Etudes Nucléaire de Saclay
Peter Walden, Ph.D.
Gif-sur-Yvette, France
Abteilung Immungenetik
Max-Plank-Institut für Biologie
Francis Schuber, Ph.D. Tübingen, Germany
Université Louis Pasteur
CNRS URA 1386 Donald F.H. Wallach, M.D., Ph.D.
Faculté de Pharmacie de Strasbourg Micro Vesicular System, Inc.
Strasbourg-Illkirch, France Nashua, New Hampshire
Claude Sirlin, PhD.
Lab de Chimie Génétique
CNRS URA 1386
Faculté de Pharmacie de Strasbourg
Illkirch, France
CONTENTS
PARTI. THE LIPOSOMES
Chapter 1
Influence of Liposome Characteristics on Their Properties and Fate......................................................3
Roger R.C. New
Chapter 2
Chemistry of Ligand-Coupling to Liposomes.........................................................................................21
Francis Schuber
Chapter 3
Non-Phospholipid Molecules and Modified Phospholipid Components of Liposomes........................41
Jean R. Philippot, Pierre Milhaud, Christophe O. Puyal, and Donald F.H. Wallach
Chapter 4
Liposomes at the Industrial Scale............................................................................................................59
Gérard Redziniak, Pierre Perrier, and Christan Marechal
PART II. LIPOSOMES AS CELL OR MEMBRANE MODELS
Chapter 5
Liposomes as Tools for the Reconstitution of Biological Systems.......................................................71
Jean-Louis Rigaud and Bruno Pitard
Chapter 6
Liposomes as Tools in Immunological Studies.......................................................................................89
Peter Walden
Chapter 7
Liposomes as Tools for Elucidating the Mechanisms of Membrane Fusion.......................................103
Nejat Düzgüne§ and Shlomo Nir
Chapter 8
Liposomes, Viruses, and Membrane Fusion..........................................................................................137
Maria C.P. de Lima and Dick Hoekstra
PART III. NEW DEVELOPMENTS OF LIPOSOMES
Chapter 9
Gene Transfer with Cationic Amphiphiles............................................................................................159
Jean-Serge Remy, Claude Sirlin, and Jean-Paul Behr
Chapter 10
Cationic Liposome-Mediated Gene Transfer In Vitro and In Vivo.....................................................171
Robert J. Debs
Chapter 11
Sterically Stabilized (Stealth®) Liposomes: Pharmacological Properties and Drug Carrying
Potential in Cancer.................................................................................................................................177
Demetrios Papahadjopoulos and Alberto A. Gabizon
Chapter 12
Liposomes as Carriers of Antigens.......................................................................................................189
Martin Friede
Chapter 13
pH-Sensitive Liposomes as Tools for Cytoplasmic Delivery..............................................................201
David Collins
Chapter 14
Liposomes as Transporters of Oligonucleotides...................................................................................215
Lee Leserman
Chapter 15
Imaging Tools: Liposomal Agents for Nuclear Medicine, Computed Tomography,
Magnetic Resonance, and Ultrasound...................................................................................................225
Colin Tilcock
Chapter 16
Non-Phospholipid Liposomes: Principles and Bulk Applications.......................................................241
Donald F.H. Wallach and Rajiv Mathur
Chapter 17
Non-Phospholipid Vesicles as Experimental Immunological Adjuvants.............................................253
Carole Varanellit S. Kumar, and Donald F.H. Wallach
Index.......................................................................................................................................................267
PARTI
The Liposomes
