Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients

EuroIntervention. 2011 Oct 30;7(6):730-7. doi: 10.4244/EIJV7I6A116.

Abstract

Aims: The vascular effects of drug- eluting balloon (DEB) deployment in the absence of coronary stents have not been characterised. This study evaluated potential vascular effects of paclitaxel-coated angioplasty balloons using different excipients in the absence of additional stents.

Methods and results: A total 45 porcine arteries were treated with paclitaxel-coated DEBs using four different excipients (all 3.0 µg/mm2): A) iopromide (n=9), B) ATEC excipient (n=8), C) BTHC excipient (n=10), D) lecithine excipient (n=10). Uncoated bare angioplasty balloons served as controls (n=8). Histology, histomorphometry, and quantitative angiography analysis were performed 28 days following intervention. Tissue concentrations of paclitaxel were measured in selected animals using BTHC excipient (n=39 arteries) and reached maximum concentrations of 165 ng/mg 30 min after delivery in coronary target tissue. There were no differences in efficacy endpoints using histomorphology or quantitative angiography between groups. In contrast, however, treatment with DEBs using BTHC excipient or iopromide was associated with increased fibrin deposition and inflammation indicating delayed vascular healing. DEBs using lecithin excipient or uncoated angioplasty balloons did not induce any comparable vascular effects.

Conclusions: Effective excipients are necessary to accomplish successful balloon facilitated paclitaxel delivery, which is associated with delayed vascular healing as a sign of successful drug transfer. The potential of DEBs to diminish restenosis following angioplasty may be insufficient in the absence of additional stents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary / instrumentation*
  • Animals
  • Butyrates / administration & dosage
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / pharmacokinetics
  • Citrates / administration & dosage
  • Coated Materials, Biocompatible*
  • Coronary Angiography
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Equipment Design
  • Excipients / administration & dosage*
  • Female
  • Iohexol / administration & dosage
  • Iohexol / analogs & derivatives
  • Lecithins / administration & dosage
  • Male
  • Models, Animal
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Sus scrofa
  • Time Factors
  • Wound Healing / drug effects

Substances

  • Butyrates
  • Cardiovascular Agents
  • Citrates
  • Coated Materials, Biocompatible
  • Excipients
  • Lecithins
  • Iohexol
  • acetyl triethyl citrate
  • iopromide
  • butyryl-n-trihexylcitrate
  • Paclitaxel