DRUG-DELIVERY INTO THE ARTERIAL-WALL - A TIME-COURSE STUDY WITH USE OF A LIPOPHILIC DYE

PURPOSE: One potential approach to the prevention of restenosis after angioplasty is to deliver antiproliferative agents directly to the ang ioplasty site. The purpose of this study was to determine the time cou rse of drug penetration into the media of the balloon-dilated artery. MATERIALS AND METHODS: Balloon angioplasty of the left and right iliac arteries was performed once for 1 minute in each of five rabbits. A d ouble-balloon catheter was then positioned at the site of angioplasty, and the fluorescent dye PKH26 (molecular weight, 961) was delivered u nder pressure to simulate drug delivery. Afterward, the arteries were removed and dye penetration into the media was measured on frozen cros s sections by epifluorescence microscopy. RESULTS: Delivery of the dye was performed for periods ranging from 5 to 50 minutes at a mean pres sure of 189 mm Hg. The depth of dye penetration (D, micrometers) was d irectly related to dye perfusion time (T, minutes) (D = 0.348T + 11.95 8, r = 0.496, P < .01). This equation predicts complete medial dye pen etration in 81 minutes assuming an average intima-media thickness (40 mu m). CONCLUSION: This study demonstrates that PKH26 can be delivered to the media of the dilated artery. However, the time required to obt ain complete penetration may limit the utility of this double-balloon catheter approach to drug delivery.