Characterization of biodegradable drug delivery vehicles with the adhesive properties of leukocytes

Abstract

The site-specific expression of selectins (E- and P-selectin) on endothelial cells of blood vessels during inflammation provides an opportunity for the targeted delivery of anti-inflammatory drugs to inflammatory sites. Previous work in our laboratory has shown that artificial capsules with the adhesive properties of leukocytes can be made by attaching leukocyte adhesive ligands to polystyrene microspheres. In this work, we have adapted this technology to create a targeted delivery system using biodegradable, poly lactic-co-glycolic-acid (PLGA) microspheres. Biotinylated-Sialyl Lewis(x) (sLe(x)), a carbohydrate that serves as a ligand to selectins, was attached to the surface of avidin-linked PLGA microspheres. These carbohydrate-coated microspheres mimic the adhesive behavior of leukocytes on selectins in flow chambers, displaying slow rolling under flow. The rolling velocities displayed by sLe(x)-coated microspheres were similar to those displayed by leukocytes rolling on P- or E-selectin coated surfaces, and these rolling velocities, which relate to the residence time of the capsules, can be tuned by changing the density of carbohydrate residues on microsphere surfaces. We have also demonstrated that these microspheres will release model drugs on a time scale of several days. Therefore, we have made a targeted drug delivery vehicle that mimics the adhesive properties of leukocytes and is biodegradable.