Drug Targeting Organ-Specific Strategies

4 Cell Specific Delivery of Anti-Inflammatory
Drugs to Hepatic Endothelial and Kupffer
Cells for the Treatment of Inflammatory
Liver Diseases
Barbro N. Melgert, Leonie Beljaars, Dirk K. F. Meijer, Klaas Poelstra
4.1 Introduction
Fibrosis or scarring of the liver occurs after damage to liver tissue. Most chronic liver diseases
eventually result in excess scarring leading to liver cirrhosis. This fatal disease, to date, can
only be effectively treated with a liver transplantation. Since this is a costly procedure, hampered
by the lack of donor organs among other technical factors, much effort has been put
into developing new drugs.The drugs available are not sufficiently effective and/or cause too
many adverse side-effects.Therefore drug targeting is an option in trying to maximize efficacy
and minimize adverse drug reactions.
Chronic liver diseases are characterized by an inflammatory and a fibrotic component,
both of which can be targets for pharmacological intervention. This chapter focuses on the
treatment of liver fibrosis through the targeting of anti-inflammatory drugs. The target cells
within the liver for anti-inflammatory treatment and possible entry mechanisms in these target
cells will be identified. In addition, the different drug carriers and drug targeting preparations
will be reviewed.
Since drug targeting implies the manipulation of drug distribution in the whole body, emphasis
should be put on in vivo studies. In contrast to in vitro studies, studies in the intact organism
will provide more definite insight into the cell specificity of carrier systems, the potential
toxicity, immunogenicity, and the ability of the carrier system to pass anatomical barriers
en route to the target cells. Moreover, it is of the utmost importance that these parameters
are also studied in the diseased state, since the targeting potential of carriers can change
dramatically under pathological conditions. In vitro studies with various liver preparations
can be used to study endocytosis, carrier degradation and intracellular release of the targeted
drug in more detail. In addition, the concept of drug targeting should also be tested in human
tissue. Possibilities to include early (kinetic) screening in human tissue will also be discussed
in this chapter.
4.2 The Liver
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)
At the crossroads between the digestive tract and the rest of the body resides the largest solid
organ of the body: the liver. Because of its interposition, the liver has a dual blood supply.