Mural delivery of iloprost with use of hydrogel-coated balloon catheters suppresses local platelet aggregation

Krishna Kandarpa, Seishi Nakatsuka, Stephen M. Bravo, Ravi S. Harapanhalli, James J. Barry

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

PURPOSE: 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. MATERIALS AND 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 μg). CONCLUSION: 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.

Original languageEnglish
Pages (from-to)997-1004
Number of pages8
JournalJournal of Vascular and Interventional Radiology
Volume8
Issue number6
DOIs
Publication statusPublished - 1997 Jan 1

Keywords

  • Arteries, transluminal angioplasty
  • Blood, platelet
  • Drugs, effects
  • Iloprost

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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