(487d) Incorporation of Statins in a Perivascular Polymeric Drug Delivery Device for the Inhibition of Intimal Hyperplasia

The primary mechanism of failure for interventional procedures like cardiac catheterization, Percutaneous Transluminal Coronary Angioplasty (PTCA) and Coronary Artery Bypass Graft (CABG) surgery is Intimal Hyperplasia (IH). IH is a chronic structural change of the vascular wall characterized by diffuse thickening of the intimal layer arising from the migration and proliferation of medial smooth muscle cells. PolyRing, developed by Kanjickal et al., is a composite polymeric device consisting of poly (DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly (ethylene glycol) (PEG) hydrogel. The drug for the treatment of IH, Cyclosporin A (CyA), was encapsulated within the PLGA microspheres.

This work focuses on modifying the PolyRing system by incorporating Simvastatin, a cholesterol lowering drug, in it. Simvastatin, obtained in a pro-drug form, when hydrolyzed to its active form, Simvastatin Acid, acts as a potent competitive inhibitor of the 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. As the focus is on controlled localized delivery, we hypothesize the need of using the active form (SVA) as against the lactone form (SV). The data from the cell culture study, which compares the efficacy of the two different forms i.e., SV and SVA in inhibiting smooth muscle cell proliferation, will be presented. The microspheres loaded with SV and SVA are fabricated using oil-water and water-oil-water emulsion techniques respectively and the device is characterized using ESEM. The environmental scanning electron micrographs suggest a uniform distribution of the microspheres in the PEG hydrogel matrix. Thus, the device, PolyRing, will have been modified for the controlled delivery of Simvastatin to inhibit IH.