Author + information
- Received March 3, 2000
- Revision received June 23, 2000
- Accepted August 7, 2000
- Published online December 1, 2000.
- Douglas E Drachman, MD∗,* (, )
- Elazer R Edelman, MD, PhD, FACC∗,†,
- Philip Seifert, MS†,
- Adam R Groothuis, MS†,
- Danielle A Bornstein, BS†,
- Kalpana R Kamath, PhD‡,
- Maria Palasis, PhD‡,
- Dachuan Yang, PhD‡,
- Sepideh H Nott, ScM‡ and
- Campbell Rogers, MD, FACC∗,†
- ↵*Reprint requests and correspondence: Dr. Douglas E. Drachman, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
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.
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.
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-Σ-caprolactone) copolymer alone or containing paclitaxel, 200 μg.
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.
Poly(lactide-co-Σ-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.
☆ Supported, in part, by grants from National Institutes of Health (GM/HL 49039, HL 60407 and HL 03104).
- Received March 3, 2000.
- Revision received June 23, 2000.
- Accepted August 7, 2000.
- American College of Cardiology