Microparticles for Targeted Drug Delivery to Inflamed Vasculature

Abstract

Purpose: : The purpose of this study was to develop a drug delivery microparticle that could selectively home to activated endothelial cells in vivo.

Methods: : Homing is achieved by surface-decorating the particles with sialyl-Lewis x (sLex), a tetrasaccharide that binds to the selectins present on activated endothelial cells. Poly (lactide-co-glycolide) (PLGA) and poly (ethylene imine) (PEI) were used as the polymer matrix to construct the particles. Coumarin-6-loaded particles were prepared by a modified water/oil/water emulsion technique and characterized for mass and size distribution. In vitro and in vivo inflammation models were used to study the homing of the particles.

Results: : In vitro data indicated that the particles could efficiently encapsulate POT-4, a potent cyclic peptide complement inhibitor, and release it over 60 days in PBS. The sLex conjugated particles preferentially bound to activated endothelial cells over resting cells, and this specific binding was decreased significantly by addition of anti-sLex antibody.

Conclusions: : sLex conjugated microparticles may be used as a drug delivery vehicle homing to the sites of inflammation.

Keywords: inflammation