MURAL DELIVERY OF ILOPROST WITH USE OF HYDROGEL-COATED BALLOON CATHETERS SUPPRESSES LOCAL PLATELET-AGGREGATION

PURPOSE: To develop reproducible and quantifiable methods for mural de livery of iloprost, a potent agent against platelet aggregation, with use of hydrogel-coated angioplasty balloons, and to determine the in v ivo effect of direct iloprost delivery on platelet aggregation at the angioplasty site. MATERIALS AND METHODS: Drug loading of tritiated ilo prost from an immersion solution onto hydrogel-coated balloons was eva luated as a function of balloon size (3 mm x 2 cm, 6 mm x 2 cm, 8 mm x 3 cm; n = 4 each), drug concentration (0.0715 mg/mL, 0.1072 mg/mL, 0. 1430 mg/mL; n = 3 each), and duration of immersion (40 seconds, 60 sec onds, 120 seconds; n = 3 each). In another set of experiments, optimal drying methods were tested to minimize drug loss within a protective delivery sheath (n = 3 each). Ex vivo angioplasty was performed on exc ised swine arteries to estimate how much of the drug present on the ba lloon could be delivered to the wall (n = 3 iliac segments). Finally, in vivo angioplasty was performed in three Yorkshire pigs (n = 6 ilopr ost-treated and 6 control arteries) and indium-111-Iabeled platelet ag gregation was measured at these sites, which were harvested 1 hour aft er the procedure. RESULTS: In the initial set of experiments, the auth ors found that the volume of drug loaded is determined by the wet-volu me of the hydrogel coating, that the majority of volume loading occurs within the first 2 minutes, and that the volume uptake is independent of the drug concentration. The optimal drying method resulting in the least loss of iloprost within the sheath (only 4%) was prolonged dryi ng (5 hours) under ambient conditions. Ex vivo angioplasty experiments showed that approximately 33% of the drug present on the balloon can be delivered to the wall. Finally, in vivo experiments showed that pla telet aggregation is significantly suppressed at treated sites (by app roximately 33% compared to control sites; P = .03) by minuscule mural doses of iloprost (roughly estimated at under 1 mu g). CONCLUSION: Qua ntifiable and reproducible methods for loading iloprost onto hydrogel- coated angioplasty balloons were developed. The best of these methods was able to deliver enough iloprost into the wall to significantly red uce local platelet aggregation.