LOCAL-DELIVERY OF DEXAMETHASONE FOR PREVENTION OF NEOINTIMAL PROLIFERATION IN A RAT MODEL OF BALLOON ANGIOPLASTY

A periadventitial polymer system is an alternative local drug delivery technique to obtain and maintain high tissue levels of the drug at th e site of vascular injury. To determine if local periadventitial deliv ery of dexamethasone decreases neointimal proliferation after balloon vascular injury, in three groups of Sprague-Dawley rats, 5% dexamethas one, 0.5% dexamethasone, and placebo silicone polymers were implanted around the left common carotid artery after balloon injury. In a fourt h group, placebo polymers were implanted without balloon injury. Dexam ethasone serum and tissue levels after polymer implantation were signi ficantly higher in the 5% dexamethasone group compared with the 0.5% d examethasone group. There was no neointima formation in any of the art erial segments covered with placebo polymers for 3 wk, but without bal loon injury. In the arterial segments covered by the 5 and 0.5% dexame thasone polymers, there was a 76 and 75% reduction in intima/media rat ios, respectively, compared with the placebo group (5% dexamethasone, 0.26 +/- 0.04; 0.5% dexamethasone, 0.27 +/- 0.03; placebo, 1.09 +/- 0. 16, respectively; P < 0.0001). These results suggest that: (a) silicon e polymers mapped around the common carotid arteries for 3 wk did not, without balloon injury, stimulate neointimal proliferation in the rat model; (b) the activity of the drug-eluting polymer for suppressing i ntimal proliferation was chiefly, but not exclusively, site specific; and (c) transadventitial local delivery of dexamethasone at two differ ent doses markedly inhibits neointimal proliferation after balloon vas cular injury.