NANOTHERAPEUTICS

Drug Delivery Concepts

in Nanoscience
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NANOTHERAPEUTICS
Drug Delivery Concepts
in Nanoscience

edited by
Alf Lamprecht
of France

PAN STANFORD PUBLISHING

Published by
Pan Stanford Publishing Pte. Ltd.
Penthouse Level, Suntec Tower 3
8 Temasek Boulevard
Singapore 038988

Email: editorial@panstanford.com
Web: www.panstanford.com

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

NANOTHERAPEUTICS
Drug Delivery Concepts in Nanoscience
Copyright 2009 by Pan Stanford Publishing Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any form or by
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ISBN 978-981-4241-02-1 (Hardcover)

ISBN 978-981-4241-16-8 (eBook)

Printed in Singapore.
In memoriam Armin Lamprecht
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 Preface

Research and development of innovative drug delivery systems are

increasing at a rapid pace throughout the world. This trend will intensify
in future as public health expenses demand lower costs and increased
efficiency for new therapies. In order to meet this demand, many well-
known and efficiently applied drugs will be reformulated in new drug
delivery systems that can be value-added for optimized therapeutic
activity.
One important aspect in the newly developing field of nanomedicine
is the use of nanoparticule drug delivery systems allowing innovative
therapeutic approaches. Nanotechnology as a delivery platform offers
very promising applications in drug delivery. Due to their small size such
drug delivery systems are promising tools in therapeutic approaches such
as selective or targeted drug delivery towards a specific tissue or organ,
enhanced drug transport across biological barriers (leading to an
increased bioavailability of the entrapped drug) or intracellular drug
delivery which is interesting in gene and cancer therapy.
The nanotechnological approaches in drug delivery include a large
variety of forms, mainly systems based on lipid or polymeric
nanoparticles (nanocapsules and nanospheres) microemulsions,
liposomes, but also polymeric micelles and cyclodextrins. Potentially
different from other scientific communities in the field of drug delivery,
nanoparticulates are defined as carrier system with a size below one
micron.
On behalf of a great team of nano researchers who have been part of
this exciting project, I am pleased to introduce to the scientific
community a comprehensive work on Nanotechnology applied in the

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field of drug delivery, which can be seen as a knowledge base for

therapeutic applications of nanotechnologies.
In the past decade, ongoing efforts have been made to develop
systems or drug carriers capable of delivering the active molecules
specifically to the intended target organ in order to increase the
therapeutic efficacy. This approach involves modifying the
pharmacokinetic profil of various therapeutic classes of drugs through
their incorporation in colloidal nanoparticulate carriers in the submicron
size range such as liposomes or nanoparticles. These site-specific
delivery systems allow an effective drug concentration to be maintained
for a longer interval the target tissue and result in decreased side effects
associated with lower plasma concentrations m the peripheral blood.
Thus, the principle of drug targeted is to reduce the total amount of drug
administered while optimizing its activity. It should be mentioned that
the scientific community is still skeptical that such goals could be
achieved since huge investments of funds and promising research studies
have in many cases resulted in disappointing results and have also been
slow in yielding successfully marketed therapeutic nanocarriers. With the
recent approval by health authorities of several effective nanosized
products containing antifungal or cytotoxic drugs, interest in small drug
carriers has been renewed.
A vast number of studies and reviews as well as several books have
been devoted to the development, characterization, and potential
applications of specific microparticulate- and nanoparticulate delivery
systems. No encapsulation process developed to date has been able to
produce the full range of capsules desired by potential capsule users. Few
attempts have been made to present and discuss in a single book the
entire therapeutic range of nanocarriers covered in this book. The general
theme and purpose here are to provide the reader with a current and
general overview of the existing nanosized delivery systems and to
emphasize the various fields of therapeutic applications. The systematic
approach used in presenting the first part introducing to the general
therapeutic options followed by disease-focused reviewing the existing
drug carriers should facilitate the comprehension of this increasingly
complex field and clarify the main considerations involved in designing
 Preface IX

manufacturing, characterizing, and evaluating a specific nanosized-

delivery system for a given therapeutic application or purpose.
The first part highlights the exceptional properties of nanoparticles
involving their sustained drug release and other physicochemical
properties, but especially their ability to trigger drug transport across
biological barriers. The general mechanisms of drug delivery, particle
translocation, interactions with cells are detailed in this part of the book.
Besides, the general strategies of nanoparticulate drug targeting and gene
therapy will be elucidated here. The first part of the book starts with a
chapter describing the physicochemical aspects of nanocarriers,
including particulate systems, liposomes, micellar systems, emulsions,
their principal properties, the main excipients necessary for their
manufacturing and the basics on their preparation techniques. The
authors also address major issues such as the stability of these
formulations as well as aspects on the final pharmaceutical form to
administer these carriers.
The following chapters deal with the general aspects on drug
transport across biological barriers, for the moment one of the most
important applications of nanocarriers in the field of therapeutics. Drugs
with low permeability properties can significantly enhance their value by
their use in a nano-formulation which increases its transport.
Another important aspect is the application of small carriers in the
area of drug targeting. This chapter elucidates the potential of
nanocarriers in order to allow specific drug delivery to inaccessible
disease sites.
The last chapter in this first part is presenting the application of
nanodevices in the field of the gene therapy. Although still today most of
the gene therapy approaches rely on the use of viral systems, more and
more studies deal with the use of non-viral gene delivery due to the
advances in the development of biomaterials.
The second part will focus specifically on the therapeutic approaches
which are possible by the use of nanocarriers dividing the overall context
into chapters dealing with diverse diseases and the relevant therapeutic
approaches based on the design of nanoparticulate drug delivery systems.
I am very grateful to all the authors who have shared my enthusiasm
and vision by contributing high quality manuscripts, on time, keeping in
x Preface

tune with the original design and theme of this work. You will not be
having this book in your hand less their dedication and sacrifice.

Editor
Alf Lamprecht
University of Franche-Comte, France
2007
 CONTENTS

Dedication v

Preface vii

Part I: General Aspects of Nanotherapeutics

Chapter 1 Nanocarriers in Drug Delivery - Design, Manufacture

and Physicochemical Properties
Christoph Schmidt and Alf Lamprecht ..................................... . 3
References 30

Chapter 2 Transport Across Biological Barriers

Noha Nafee, Vivekanand Bhardwaj and Marc Schneider ......... . 39
References 56

Chapter 3 Targeting Approaches

Sandrine Cammas-Marion ........................................................ . 67
References 86

Part II: Disease-Related Approaches by Nanotherapeutics ..................... 91

Chapter 4 Nanoscale Cancer Therapeutics

Yann Pellequer and Alf Lamprecht ............................................ 93
References 116

Chapter 5 Nanotherapeutics for Skin Diseases

Nicolas Atrux-Tallau, Franr;;oise FaIson and Fabrice Pirat ...... 125
References .................................................................................................... 153

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xii Contents

Chapter 6 NanoparticIes for Oral Vaccination

Juan M. Irache, Hesham H. Salman, Sara Gomez
and Carlos Gamazo ................................................................... 163
References 189

Chapter 7 NanoparticIes: Therapeutic Approaches for Bacterial

Diseases
Brice Moulari ............................................................................. 199
References 220

Chapter 8 NanoparticIe Therapy in Parasites Diseases: Possibility

and Reality!
Malika Larabi ......................... ..................... ......................... ..... 227
References 253

Chapter 9 Nanocarriers in the Therapy of Inflammatory Disease

Aif Lamprecht ............................................................................ 261
References 273

Index 277