Drug delivery into the arterial wall: a time-course study with use of a lipophilic dye.
OBJECTIVE
One potential approach to the prevention of restenosis after angioplasty is to deliver antiproliferative agents directly to the angioplasty site. The purpose of this study was to determine the time course of drug penetration into the media of the balloon-dilated artery.


METHODS
Balloon angioplasty of the left and right iliac arteries was performed once for 1 minute in each of five rabbits. A double-balloon catheter was then positioned at the site of angioplasty, and the fluorescent dye PKH26 (molecular weight, 961) was delivered under pressure to simulate drug delivery. Afterward, the arteries were removed and dye penetration into the media was measured on frozen cross sections by epifluorescence microscopy.


RESULTS
Delivery of the dye was performed for periods ranging from 5 to 50 minutes at a mean pressure of 189 mm Hg. The depth of dye penetration (D, micrometers) was directly related to dye perfusion time (T, minutes) (D = 0.348T + 11.958, r = 0.496, P < .01). This equation predicts complete medial dye penetration in 81 minutes assuming an average intima-media thickness (40 microns).


CONCLUSIONS
This study demonstrates that PKH26 can be delivered to the media of the dilated artery. However, the time required to obtain complete penetration may limit the utility of this double-balloon catheter approach to drug delivery.
Consigny
P M
PM
Department of Radiology, Gibbon, Thomas Jefferson University Hospital, Philadelphia, PA 19107.
Miller
K T
KT
D000800:Angioplasty, Balloon / Q000295:instrumentation; D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006965:Hyperplasia / Q000517:prevention & control; D007083:Iliac Artery; D009930:Organic Chemicals; D011817:Rabbits; D012008:Recurrence; D013997:Time Factors; D017539:Tunica Intima; D017540:Tunica Media
D005456:Fluorescent Dyes; D009930:Organic Chemicals; C070080:PKH 26