Drug Targeting Organ-Specific Strategies

7 Vascular Endothelium in Inflamed Tissue
as a Target for Site Selective Delivery
of Drugs
Maaike Everts, Astrid J. Schraa, Lou F. M. H. de Leij, Dirk K. F. Meijer, Grietje Molema
7.1 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)
Chronic inflammatory disorders are characterized by an abundant leucocyte infiltration in
the affected tissue due to the continuous recruitment of these inflammatory cells. Although
these events are part of the body’s defence mechanisms, excessive responses occur in the vicious
circle of cell activation and cell destruction, leading to acute and chronic inflammatory
disorders. Many current therapeutic approaches are based on attempts to control leucocyte
activation. Recently there has been a growing interest in the role of the endothelial cells in
leucocyte recruitment and the possibility of manipulating endothelial cell activation as a
therapeutic approach [1,2]. The endothelium plays an important role in the inflammatory
cascade, and has the advantage of being easily accessible for drug targeting preparations due
to direct contact with the blood as well as the presence of endocytotic processes [3]. Therefore
endothelial cells are attractive targets for cell-selective pharmacological intervention
employing drug targeting strategies.
The aim of this chapter is to describe potential target epitopes on endothelial cells in
chronic inflammation, the design of targeting devices on the basis of this knowledge and the
use of these targeting devices in the intervention of endothelial cell activation. Several in
vitro and in vivo test models for studying endothelial cell responses in inflammation are currently
available and will be briefly described. Since drug targeting to the inflamed endothelium
is a relatively new approach, the number of research reports dedicated to this topic is, at
present, relatively small. Therefore, this chapter will include some general considerations regarding
drug targeting to the activated endothelial cell. Adequate cell-selective delivery of
potent anti-inflammatory agents may provide an important tool for increasing the efficacy
and reducing the side-effects of such agents in the treatment of chronic inflammatory diseases.
7.2 Regulation of Immune Responses in (Chronic)
Inflammation
7.2.1 Induction of an Immune Response
After an antigen (a ‘non-self’ molecular entity) has entered the body, it is recognized by the
cells of the immune system.An important step in eliciting an efficient immune response to an