Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months

J Am Coll Cardiol. 2000 Dec;36(7):2325-32. doi: 10.1016/s0735-1097(00)01020-2.


Objectives: The purpose of this study was to determine long-term effects of stent-based paclitaxel delivery on amount, rate and composition of neointimal thickening after stent implantation.

Background: Paclitaxel prevents vascular smooth muscle cell proliferation and migration in vitro and in vivo. These actions, coupled with low solubility, make it a viable candidate for modulating vascular responses to injury and prolonged effects after local delivery. We asked whether local delivery of paclitaxel for a period of weeks from a stent coated with a bioerodible polymer could produce a sustained reduction in neointimal hyperplasia for up to six months after stenting.

Methods: Stainless steel stents were implanted in the iliac arteries of rabbits after endothelial denudation. Stents were uncoated or coated with a thin layer of poly(lactide-co-sigma-caprolactone) copolymer alone or containing paclitaxel, 200 microg.

Results: Paclitaxel release in vitro followed first-order kinetics for two months. Tissue responses were examined 7, 28, 56 or 180 days after implantation. Paclitaxel reduced intimal and medial cell proliferation three-fold seven days after stenting and virtually eliminated later intimal thickening. Six months after stenting, long after drug release and polymer degradation were likely complete, neointimal area was two-fold lower in paclitaxel-releasing stents. Tissue responses in paclitaxel-treated vessels included incomplete healing, few smooth muscle cells, late persistence of macrophages and dense fibrin with little collagen.

Conclusions: Poly(lactide-co-sigma-caprolactone) copolymer-coated stents permit sustained paclitaxel delivery in a manner that virtually abolishes neointimal hyperplasia for months after stent implantation, long after likely completion of drug delivery and polymer degradation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Coronary Disease / pathology
  • Coronary Disease / prevention & control*
  • Drug Delivery Systems*
  • Paclitaxel / administration & dosage*
  • Rabbits
  • Recurrence
  • Stents*
  • Time Factors
  • Tunica Intima / drug effects
  • Tunica Intima / pathology*


  • Angiogenesis Inhibitors
  • Paclitaxel