Site-specific delivery of colchicine in rat carotid artery model of restenosis

A periadventitinI polymeric drug delivery system is one strategy for obtaining and maintaining high tissue levels of drugs at the site of vascular injury. The inhibitory effect of colchicine, an antiproliferative agent, on neointimal proliferation after vascular injury was examined in the balloon catheter carotid artery injury model in rats. Controlled-release colchicine delivery was achieved by formulating drug-containing ethylene vinylacetate copolymer matrices, and the release kinetics were determined in vitro and in vivo. Polymeric matrices containing 0.1% and 0.01% colchicine, and plain polymers were implanted perivascularly in rats following balloon catheter injury. The arterial specimens were harvested after 21 days, processed histologically and evaluated morphometrically. Site-specific delivery of colchicine from 0.1% loaded perivascular matrices, but not 0.01%, significantly inhibited neointimal proliferation after balloon injury. However, local tissue toxicity was observed in some animals. The results of this study should be reconfirmed in a larger animal model such as the porcine catheter injured artery model.