SITE-SPECIFIC DELIVERY OF COLCHICINE IN RAT CAROTID-ARTERY MODEL OF RESTENOSIS

A periadventitial polymeric drug delivery system is one strategy for o btaining and maintaining high tissue levels of drugs at the site of va scular injury. The inhibitory effect of colchicine, an antiproliferati ve agent, on neointimal proliferation after vascular injury was examin ed in the balloon catheter carotid artery injury model in rats. Contro lled-release colchicine delivery was achieved by formulating drug-cont aining ethylene vinylacetate copolymer matrices, and the release kinet ics were determined in vitro and in vivo. Polymeric matrices containin g 0.1% and 0.01% colchicine, and plain polymers were implanted perivas cularly in rats following balloon catheter injury. The arterial specim ens were harvested after 21 days, processed histologically and evaluat ed morphometrically. Site-specific delivery of colchicine from 0.1% lo aded perivascular matrices, but not 0.01%, significantly inhibited neo intimal proliferation after balloon injury. However, local tissue toxi city was observed in some animals. The results of this study should be reconfirmed in a larger animal model such as the porcine catheter inj ured artery model.