Controlled drug delivery systems for perivascular application and intimal hyperplasia prevention

Intimal hyperplasia (IH) is a pathophysiological process developing in venous grafts, commonly used to bypass circulation blocked by atherosclerosis. IH causes graft failure with life-threatening consequences. IH occurs in three stages: hyper-acute, acute, and chronic over 6 to 8 weeks. The aim of the present thesis was to develop a perivascular drug delivery system for localized prevention of IH with atorvastatin. To increase the residence time at the injury sites, hyaluronic acid was derivatized with dopamine, and a novel cross-linking mechanism was suggested. To optimize drug release profile, atorvastatin was encapsulated into biodegradable polymer by spray-drying. The microspheres showed activity towards synthetic vascular smooth muscle cells in vitro. The device showed a burst release phase to target IH in the hyper-acute stage, followed by a sustained release to supply the drug continuously over several weeks, and demonstrated biocompatibility in vivo