Abstract 4403: Stent-based Liposomal Gene Delivery: Characterization of Target Cell Population, Pattern of Expression and Therapeutic Potential of Lipostents
Although a successful tool in the interventional cardiologist’s armamentarium, drug eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Early regeneration of the endothelial layer is desirable as it protects against catastrophic in-stent thrombosis. Gene eluting stents are a potential alternative as they may allow selective inhibition of neointimal formation whilst promoting endothelial regeneration. Our group and other investigators have already shown that adenoviral gene delivery from stents is a promising strategy for efficient gene delivery and that adenoviral eNOS delivery can result in significantly decreased neoinitmal formation and enhanced re-endothelialisation. However, there are biosafety concerns over the use of viral gene delivery. Therefore, we examined the use of non-viral gene delivery methods from a stent using liposomes. We coated liposomes directly onto the surface of a phosphorylcholine-coated stent. These lipostents were then deployed in the injured external iliac artery of hypercholesterolemic New Zealand white rabbits and recovered after 28 days. Liposomal formulations containing the reporter lacZ gene and therapeutic eNOS genes were used. Our results demonstrated highly efficient gene delivery using this system at 28 days post-deployment: 21.3±7.5% in the media and 26.8±11.2% in the neointima. In contrast to adenoviral delivery which delivers to smooth muscle cells at the struts, liposomal delivery resulted in expression in macrophages outside of the stent struts. Despite the alternate cell population targeted, liposomal eNOS delivery resulted in improved re-endothelialization (17.52±12.86 vs 47.53±9.54) with reduced media/neointima ratio (8.06±3.8 vs 15.16±9.2) compared to controls (p<0.05 for both). Our results suggest that the use of liposomes for gene delivery from stents results in highly efficient gene delivery to an alternate cell population compared with adenoviral gene delivery and the use of liposomal eNOS is a promising strategy for treating in-stent restenosis.