(590g) A Vascular Paint for Local Delivery of Therapeutics to Atherosclerotic Plaques

The rupture of atherosclerotic plaques and the subsequent formation of blood clots is a major cause of strokes and heart attacks. Developing therapies that locally treat plaques and make them less vulnerable to rupture is an important goal for preventing these cardiovascular events. We synthesized adhesive hydrogels that can be painted on the inside of blood vessels to use as a physical barrier for preventing plaque rupture and as a drug depot for delivering therapeutics to the vessel wall. These hydrogels are composed of inert polysaccharides coupled to catechol moieties, which have strong adhesive characteristics that mimic the adhesive components of marine mussels. Using microfluidic devices in vitro we found that these hydrogels can be painted on endothelial cells and remain adhered at shear stresses higher than the physiological range of shear stresses in blood vessels. Using a catheter-based approach the hyrdogels could be painted in sub-millimeter size patches on the walls of arteries of mice and remained adhered for over four months. The hydrogel could also be painted on atherosclerotic plaques in a mouse model of atherosclerosis. Small molecules could be released from degradable PLGA particles that were blended in the paint and taken up into the vessel wall. These results suggest that this vascular paint may have applications as a local therapy for treating at-risk atherosclerotic plaques and other diseased area of the vasculature.