Low-dose paclitaxel elution by novel bioerodible sol-gel coating on stents inhibits neointima with low toxicity in porcine coronary arteries

Int J Cardiol. 2009 Jun 12;135(1):93-101. doi: 10.1016/j.ijcard.2008.06.030. Epub 2008 Aug 9.

Abstract

Objectives: The present study was designed to evaluate a novel bioerodible sol-gel film coated paclitaxel-eluting stent (sol-gel-PES, 3 microg per stent) in a porcine coronary artery model.

Background: Although current polymer-based PES decrease restenosis, the permanent polymer and bound drug have raised concerns regarding delayed vessel healing and late stent thrombosis.

Methods: Polymer-based PES (poly-PES, n = 8), sol-gel-PES (n = 15), bare metal (BMS, n = 14), and sol-gel film only (sham, n = 12), stents were implanted in 17 juvenile pigs. Animals were terminated 28 days post-implant for angiographic restudy and complete histopathologic and histomorphometric analyses.

Results: Angiographic late loss was equally reduced for both poly-PES and sol-gel-PES (0.51 +/- 0.64 and 0.61 +/- 0.52 mm, respectively) compared to both BMS and sham (0.98 +/- 0.74 and 1.25 +/- 0.72 mm, p < 0.05). Similarly beneficial results were observed for histomorphometric parameters of neointimal thickness and area, yielding reductions of in-stent stenosis by 43% and 48% for poly-PES, as well as 31% and 37% for sol-gel-PES, vs. BMS and sham, respectively (p < 0.05). Re-endothelialization was complete in all groups. Although the inflammatory cell infiltration and intramural thrombus scores were no different between poly- and sol-gel-PES, medial necrosis was increased for poly-PES (p < 0.05 vs. all others).

Conclusions: A novel bioerodible sol-gel film coated with low-dose paclitaxel demonstrates less toxicity to the coronary tunica media, while retaining effective inhibition of neointimal formation at 28 days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Angiography
  • Coronary Restenosis / prevention & control*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / pathology*
  • Dose-Response Relationship, Drug
  • Drug-Eluting Stents*
  • Female
  • Gels
  • Male
  • Necrosis
  • Paclitaxel / pharmacokinetics*
  • Paclitaxel / toxicity
  • Polymers
  • Sus scrofa
  • Tubulin Modulators / pharmacokinetics*
  • Tubulin Modulators / toxicity
  • Tunica Intima / drug effects
  • Tunica Intima / pathology

Substances

  • Gels
  • Polymers
  • Tubulin Modulators
  • Paclitaxel