LOCALIZED INTRAMURAL DRUG-DELIVERY DURING BALLOON ANGIOPLASTY USING HYDROGEL-COATED BALLOONS AND PRESSURE-AUGMENTED DIFFUSION

Objectives. This study was designed to assess the feasibility of using hydrogel-coated balloons to deliver biologically active agents to the blood vessel wall. Background. The local intramural delivery of thera peutic agents during balloon angioplasty has been proposed as an adjun ctive technique for preventing early intracoronary thrombosis and late restenosis. Methods. To assess the efficacy of delivery and depth of penetration in vitro, local delivery of horseradish peroxidase was per formed in 40 porcine peripheral arteries, and delivery of fluoresceina ted heparin was performed in 20 porcine peripheral arteries and 7 huma n atheromatous arteries. To determine the persistence of these agents in the vessel wall in vivo, horseradish peroxidase was delivered to 18 porcine peripheral arteries that were harvested at intervals of 45 mi n to 48 h. Fluoresceinated heparin was delivered to 22 porcine periphe ral arteries, 14 with the use of a protective sleeve, harvested at int ervals of 30 s to 24 h. Results. In vitro agent delivery was successfu l in all specimens. The depth of penetration of horseradish peroxidase was directly related to both balloon pressure (p < 0.04) and duration of inflation (p < 0.01), In vivo peroxidase staining was evident at 4 5 and 90 min but not thereafter. With the use of a protective sleeve, heparin was present in all arteries harvested at 30 s, with marked dis sipation at 1 and 24 h. Without a sleeve, no fluorescein staining was detected in any artery. With both agents, delivery occurred consistent ly over broad regions of the vessel wall that were free of architectur al disruption. Conclusions. Hydrogel coated balloons can deliver biolo gically active agents to the vessel wall without gross tissue disrupti on and may provide an atraumatic method for the local delivery of ther apeutic agents during balloon angioplasty.