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Liposome Technology
Third Edition
Volume I
Liposome Preparation
and Related Techniques
Edited by
Gregory Gregoriadis
The School of Pharmacy
University of London
and
Lipoxen PLC
London, U.K.
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.
No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic,
mechanical, or other means, now known or hereafter invented, including photocopying, microfilming,
and recording, or in any information storage or retrieval system, without written permission from the
publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.
com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood
Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and
registration for a variety of users. For organizations that have been granted a photocopy license by the
CCC, a separate system of payment has been arranged.
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 Informa Web site at
www.informa.com
T&F_LOC_G_Master.indd
DK8821_C000a.indd 4 1 08/08/2006
6/21/06 9:14:48
2:51:56 AM
PM
Dedicated to the memory of my parents,
Christos and Athena
Preface
Preface
,,
The science and technology of liposomes as a delivery system for drugs and
vaccines have evolved through a variety of phases that I have been privileged
to witness from the very beginning. The initial observation (1) that exposure
of phospholipids to excess water gives rise to lamellar structures that are able
to sequester solutes led to the adoption of these structures (later to become
known as liposomes) as a model for the study of cell membrane biophysics.
Solute sequestration into liposomes prompted a few years later the develop-
ment of the drug delivery concept (2,3) and, in 1970, animals were for the first
time injected with active-containing liposomes (3,4). Subsequent work in
the author’s laboratory and elsewhere worldwide on drug- and vaccine-
containing liposomes and their interaction with the biological milieu
in vivo culminated in the licensing of a number of injectable liposome-based
therapeutics and vaccines. The history of the evolution of liposomes from
a structural curiosity in the 1960s to a multifaceted, powerful tool for
transforming toxic or ineffective drugs into entities with improved pharma-
cological profiles today has been summarized elsewhere (5,6).
The great strides made toward the application of liposomes in the
treatment and prevention of disease over nearly four decades are largely
due to developments in liposome technology; earlier achievements were
included in the previous two editions of this book (7,8). The avalanche of
new techniques that came with further expansion of liposomology since
v
vi Preface
the second edition in 1992 has necessitated their inclusion into a radically
updated third edition. Indeed, so great is the plethora of the new material
that very little from the second edition has been retained. As before, con-
tributors were asked to emphasize methodology employed in their own
laboratories since reviews on technology with which contributors have no
personal experience were likely to be superficial for the purpose of the
present book. In some cases, however, overviews were invited when it was
deemed useful to reconnoiter distinct areas of technology. A typical chapter
incorporates an introductory section directly relevant to the author’s subject
with concise coverage of related literature. This is followed by a detailed
methodology section describing experiences from the author’s laboratory
and examples of actual applications of the methods presented, and, finally,
by a critical discussion of the advantages or disadvantages of the methodol-
ogy presented vis-a-vis other related methodologies. The 55 chapters
contributed have been distributed logically into three volumes. Volume I
deals with a variety of methods for the preparation of liposomes and an
array of auxiliary techniques required for liposome characterization and
development. Volume II describes procedures for the incorporation into
liposomes of a number of drugs selected for their relevance to current trends
in liposomology. Volume III is devoted to technologies generating
liposomes that can function in a ‘‘targeted’’ fashion and to approaches of
studying the interaction of liposomes with the biological milieu.
It has again been a pleasure for me to undertake this task of bringing
together so much knowledge, experience, and wisdom so generously pro-
vided by liposomologist friends and colleagues. It is to be hoped that the
book will prove useful to anyone involved in drug delivery, especially those
who have entered the field recently and need guidance through the vastness
of related literature and the complexity and diversity of aspects of liposome
use. I take this opportunity to thank Mrs. Concha Perring for her many
hours of help with the manuscripts and Informa Healthcare personnel for
their truly professional cooperation.
Gregory Gregoriadis
REFERENCES
1. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the
lamellae of swollen phospholipids. J Mol Biol 1965; 13:238.
2. Gregoriadis G, Leathwood PD, Ryman BE. Enzyme entrapment in liposomes.
FEBS Lett 1971; 14:95.
3. Gregoriadis G, Ryman BB. Fate of protein-containing liposomes injected into
rats. An approach to the treatment of storage diseases. Eur J Biochem 1972;
24:485.
Preface vii
ix
x Acknowledgments
Preface . . . . v
Acknowledgments . . . . ix
Contributors . . . . xvii
xi
xii Contents
Conclusions . . . . 31
References . . . . 32
Mais chut !
Il paraît que sans songer à mal, j’ai pris un train de pèlerins.
Le train brûle Gênes, dédaigne Pise, laisse Florence ; nous
allons droit à Rome faire nos Pâques.
En face de moi, un gros abbé : l’air réjoui du voyageur, l’œil
grave du conducteur d’âmes.
Il prend le coin, s’installe et se carre. Tout le monde se gêne et
me gêne pour lui. Il accepte de bonne grâce.
Moi je n’ai garde de protester, me rappelant cette admirable
prescription de la civilité puérile et honnête : « Si vous vous trouvez
à table à côté d’un ecclésiastique, ayez pour lui les mêmes égards et
les mêmes prévenances que pour une dame. » Ayons donc des
égards et des prévenances ; ce qui est d’obligation à table doit l’être
également en wagon.
M. l’abbé ferme les yeux, médite ou feint de méditer ; puis, tout à
coup, énergiquement, il me tire un sac d’entre les jambes, et le pose
sur ses genoux, un peu sur les miens. Le sac est violet, en peluche
ancienne comme on en voit au dos des fauteuils. M. l’abbé ouvre le
sac, suivi dans ses moindres mouvements par l’œil sympathique des
dévotes, il en sort une chancelière, de même étoffe et violette aussi,
puis une calotte qui est noire, mais garnie de violet à l’intérieur
comme les poches de la soutane.
J’entends les dévotes se dire que M. l’abbé est illustre
prédicateur quelque part entre Tarascon et Narbonne, qu’il va voir le
pape au Vatican et qu’il reviendra de là bas au moins évêque in
partibus.
Voilà qui explique cette orgie de violet chez un simple prêtre :
dans son impatience d’avoir la pourpre, le saint homme en double
ses soutanes et ses calottes, peut-être en double-t-il ses bas ! Cela
ne fait de mal à personne, et donne en attendant un petit air
d’évêque quand par suite d’un hasard heureux d’un coup de vent ou
d’un geste habile, un peu de violet montre son nez.
Les dévotes, il y en a de charmantes dans le nombre, l’admirent
d’abord en silence, mais bientôt elles s’enhardissent. On cause de
Rome naturellement, de Rome et de la semaine sainte ! M. l’abbé
explique Saint-Pierre, immense et qui paraît petit. Les dévotes d’un
commun accord, déclarent cela admirable.
— Et l’orteil de bronze qu’on baise ! et près de Sainte-Marie-
Majeure, la Scala santa que l’on ne monte qu’à genoux ?
Elles voudraient toutes déjà baiser l’orteil et user de leurs genoux
les degrés de la Scala santa.
— Est-il vrai, qu’on parle dans les églises, que les curés vont au
café et qu’ils donnent l’absolution du bout d’une gaule ?
Sur ces jolies lèvres, dans ce gazouillis, la religion prend un air
aimable. Hélas ! que ne suis-je croyant !…
Puis, c’est la mantille.
— Quelle mantille ?
— Comment, ma chère, vous ignorez ! Mais on ne peut pas se
présenter devant Sa Sainteté sans mantille… J’en ai une toute prête
dans ma malle, très coquette, en filet de soie… D’ailleurs, il est facile
de s’en procurer à Rome… n’est-ce pas, monsieur l’abbé ?
Et voilà toutes les têtes en l’air. Cette nouvelle qu’il faut une
mantille se répand de compartiment en compartiment, de wagon en
wagon, jusqu’au bout du train. Nous allons traverser des villes,
côtoyer des fragments de golfe paraissant puis disparaissant par les
intervalles bleus de quatre-vingt-sept tunnels, suivre l’Apennin, dont
les découpures font de si fins arrière-plans aux rudes plaines
d’Étrurie ; mais nous ne voyons rien de tout cela : désormais et
jusqu’à Rome, dans les buffets des gares italiennes, épluchant des
oranges et buvant le chianti ou l’orvieto dans d’élégants petits
flacons revêtus de paille et de jonc tressé, il ne s’agira que de
mantilles.
Le soir même de notre arrivée, à une table d’un café du Corso,
où pendant la semaine sainte les gens pieux et altérés peuvent tout
à la fois écouter le Stabat de Rossini et prendre des glaces, je revis
l’abbé aux doublures violettes en compagnie de ses dévotes.
Elles, songeant à leurs mantilles et méditant de jolis plis,
essayaient des poses à l’espagnole ; lui, regardant sa main grasse
et blanche, croyait y voir luire l’améthyste ; et je compris alors, on ne
s’instruit bien qu’en voyageant, pourquoi tant d’abbés en bon point et
tant de jolies femmes vont à Rome.
VII
FLANERIE DANS ROME.
FIN.
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