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Updated: Sep 30, 2026
Design of a Biocompatible Drug-Eluting Tracheal Stent in Mice with Laryngotracheal Stenosis
Published on: January 21, 2020
Twenty-eight-day efficacy and phamacokinetics of the sirolimus-eluting stent
Bruce D Klugherz1, Gerard Llanos, Warren Lieuallen
1Laboratory for Experimental Cardiology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
Background:
In-stent restenosis is caused by neointimal hyperplasia. Sirolimus (rapamycin; Wyeth Research, Radnor, Pennsylvania, USA) inhibits vascular smooth muscle cell proliferation and we evaluated the efficacy of sirolimus in reducing neointimal formation in a rabbit iliac model and in-vivo pharmacokinetics in the porcine coronary model.
Design:
Randomized, blinded, prospective animal study.
Methods:
Bilateral rabbit iliac artery stent implantation was performed using crossflex stents (Cordis Corporation, Warren, New Jersey, USA) coated with sirolimus incorporated in a nonerodable polymer. Arteries were randomized to one of four stent groups: uncoated stents (n = 8); polymer control stents (n = 10); low-dose sirolimus-eluting stents (n = 9); and high-dose sirolimus-eluting stents (n = 10). Histomorphometry was performed at 28 days. Arterial tissue and stents were retrieved at 8, 14 and 28 days and blood samples were obtained daily during the first week.
Results:
Treatment with low-dose sirolimus was associated with a 23% (P = NS) reduction in neointimal area and treatment with high-dose sirolimus with a 45% (P < 0.05) reduction. Sustained drug release from the stent and prolonged intramural arterial deposition were confirmed for up to 28 days. No detectable sirolimus was found in the blood after 2 days.
Conclusion:
Controlled-release local delivery of a cell-cycle inhibitor from a nonerodable polymer-coated stent reduced neointimal formation in rabbit iliac arteries in a dose-dependent manner and represents a promising strategy for preventing restenosis.
Insights
Sirolimus-eluting stents significantly reduced neointimal hyperplasia in a rabbit iliac artery model. This drug-eluting stent strategy shows promise for preventing in-stent restenosis.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biomedical Engineering
Background:
- In-stent restenosis is a significant complication following angioplasty, primarily driven by neointimal hyperplasia.
- Sirolimus (rapamycin) is known to inhibit vascular smooth muscle cell proliferation, a key factor in neointimal formation.
Purpose of the Study:
- To evaluate the efficacy of sirolimus-eluting stents in reducing neointimal formation in a rabbit iliac artery model.
- To assess the in-vivo pharmacokinetics of sirolimus released from stents in a porcine coronary model.
Main Methods:
- A randomized, blinded, prospective animal study involving bilateral rabbit iliac artery stent implantation.
- Four groups were studied: uncoated stents, polymer control stents, low-dose sirolimus-eluting stents, and high-dose sirolimus-eluting stents.
- Histomorphometry was performed at 28 days post-implantation.
Main Results:
- High-dose sirolimus-eluting stents demonstrated a significant 45% reduction in neointimal area (P < 0.05).
- Low-dose sirolimus-eluting stents showed a 23% reduction, though not statistically significant (P = NS).
- Sustained sirolimus release and arterial deposition were observed for up to 28 days, with no detectable blood levels after 2 days.
Conclusions:
- Controlled, local delivery of sirolimus from non-erodable polymer-coated stents effectively reduces neointimal formation in a dose-dependent manner.
- This approach represents a promising strategy for the prevention of in-stent restenosis.
- The findings support the development of drug-eluting stents for improved cardiovascular outcomes.
