Mural delivery of iloprost with use of hydrogel-coated balloon catheters suppresses local platelet aggregation.
OBJECTIVE
To develop reproducible and quantifiable methods for mural delivery of iloprost, a potent agent against platelet aggregation, with use of hydrogel-coated angioplasty balloons, and to determine the in vivo effect of direct iloprost delivery on platelet aggregation at the angioplasty site.


METHODS
Drug loading of tritiated iloprost from an immersion solution onto hydrogel-coated balloons was evaluated 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 seconds, 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 excised swine arteries to estimate how much of the drug present on the balloon could be delivered to the wall (n = 3 iliac segments). Finally, in vivo angioplasty was performed in three Yorkshire pigs (n = 6 iloprost-treated and 6 control arteries) and indium-111-labeled platelet aggregation was measured at these sites, which were harvested 1 hour after the procedure.


RESULTS
In the initial set of experiments, the authors found that the volume of drug loaded is determined by the wet-volume 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 drying (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 platelet aggregation is significantly suppressed at treated sites (by approximately 33% compared to control sites; P = .03) by minuscule mural doses of iloprost (roughly estimated at under 1 microg).


CONCLUSIONS
Quantifiable 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 reduce local platelet aggregation.
Kandarpa
K
K
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Nakatsuka
S
S
Bravo
S M
SM
Harapanhalli
R S
RS
Barry
J J
JJ
D000800:Angioplasty, Balloon / Q000295:instrumentation*; D000818:Animals; D017536:Carotid Artery, Common; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005263:Femoral Artery; D007083:Iliac Artery; D016285:Iloprost / Q000008:administration & dosage* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015203:Reproducibility of Results; D013552:Swine
D010975:Platelet Aggregation Inhibitors; D016285:Iloprost