Drug Targeting Organ-Specific Strategies

1 Drug Targeting: Basic Concepts and Novel
Advances
Grietje Molema
1.1 Introduction
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)
Since the early 1960s, many scientists have dedicated their research to the development of
drug targeting strategies for the treatment of disease. In general, the aim of targeted therapies
is to increase the efficacy and reduce the toxicity of drugs. The behaviour of the carrier
molecules largely determines the pharmacokinetics and cellular distribution of the drug. Furthermore,
selective delivery into the target tissue may allow a higher drug concentration at or
in the target cells or even in specific compartments of the target cells. As a result, drug efficacy
can be enhanced.
Whereas the majority of strategies studied so far have incorporated cytotoxic drugs for the
treatment of cancer, it is believed that novel pharmacologically active substances will become
more and more subject to study in the coming years. With the advent of molecular biological
techniques, molecular mechanisms of disease become unravelled at an almost uncontrollable
pace. As a result, new chemical entities (NCE) are generated that in principle can exert potent
effects on disease processes but have a deficient distribution to the areas of disease. In
addition, they can be highly toxic upon gaining access to healthy tissue.The chemical characteristics
of NCEs may be such, that access to the site of action, in particular intracellular target
enzyme systems, is minimal. By attaching an NCE to a carrier molecule, its whole body
and cellular disposition can be considerably manipulated. Similarly, therapeutic macromolecules,
gene transcription/translation modulating agents such as antisense oligonucleotides
and genes themselves will progressively gain territory in the field of drug development. For
these treatment modalities to become major successes, the delivery and/or targeting of these
compounds will be an essential component [1].
The aim of this chapter is to introduce the basic principles of drug targeting as they have
evolved over previous decades. The most important chemical features and biological behavioural
characteristics of the carrier molecules exploited for drug targeting purposes will be
addressed. Novel advances in the understanding of cellular routing of naturally-occurring entities
such as viruses have in recent years been applied for cellular delivery purposes. Furthermore,
a selection of drug targeting preparations that are either in the stage of clinical
testing or have been approved for application in the clinic is discussed. As the basis of drug
development lies in the understanding of the molecular basis of diseases, selective interference
with regulatory processes in health and disease by drug targeting will become a powerful
technology. Drug targeting can, in this respect, serve both as a therapeutic approach and
as a research tool in unravelling the functions of these processes in normal physiology and
under pathophysiological conditions.