Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases

Abstract

Limitations in therapy induced by adverse effects due to unselective drug availability and therefore the use of potentially too high doses are a common problem. One prominent example for this dilemma are inflammatory diseases. Colloidal carriers allow one to improve delivery of drugs to the site of action and appear promising to overcome this general therapeutic drawback. Specific uptake of nanoparticles by immune-related cells in inflamed barriers offers selective drug targeting to the inflamed tissue. Here we focus on nanocarrier-based drug delivery strategies for the treatment of common inflammatory disorders like rheumatoid arthritis, multiple sclerosis, uveitis or inflammatory bowel disease.

Figure 1.

Adhesion of a nanoparticle on pseudopods of a macrophage imaged by transmission electron microscopy (8500×; von Briesen et al. 2006).

Figure 2.

Cell-adhesion molecules (CAMs) are involved in the adhesion of leukocytes to endothelial cells. Before leukocytes can migrate into surrounding tissue they roll on edothelial cells and subsequently arrest to the cell surface. The initial capture and rolling of leukocytes is mediated by the interaction of selectin molecules present on both leukocytes (L-selectin) and endothelial cells (P-selectin and E-selectin) with carbohydrate ligands on the reciprocal cell-surface membrane. Also, interactions between leukocyte integrins and vascular cell adhesion molecule 1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on the endothelium can mediate rolling of leukocytes. Leukocyte integrin molecules are activated by chemoattractants on the endothelial surface leading to a subsequent arrest of rolling leukocytes. Integrin receptors interact with endothelial counter-receptors of the immunoglobulin superfamily intercellular adhesion molecule 1 (ICAM-1), ICAM-2, VCAM-1 and MAdCAM-1 (Ulbrich et al. 2003). As a consequence, nanoparticulate carriers coupled with monoclonal antibodies or synthetic compounds can easily adhere to cells involved in the extravasation process instead of leukocytes.

Figure 3.

Microscopical images of a rat colon section through a tissue sample (a) of a healthy control group and (b) of a colitis group showing a typical ulceration in the colon. Confocal laser scanning microscopy of colon cross sections evidenced a distinct increase of particle adhesion from (c) the healthy control group to (d) the colitis group after administration of 100 nm particles (Lamprecht et al. 2001a).