Objectives: This study sought to assess the feasibility, safety and efficacy of sustained intracoronary delivery of dexamethasone by a novel polymer-coated eluting stent.
Background: Development of techniques to provide sustained local drug delivery has focused on polymers as matrices for drug incorporation and elution.
Methods: A tantalum wire stent was coated with dexamethasone (0.8 mg) suspended in a matrix of either low (approximately 80 kD) or high (approximately 321 kD) molecular weight poly-L-lactic acid (PLLA [0.4 mg]). Uncoated stents, stents coated with PLLA or stents coated with dexamethasone in PLLA were overexpanded by 30% to the normal vessel diameter in the coronary arteries of juvenile farm pigs. Animals were euthanized 28 days later, and neointimal thicknesses were measured. Additional pigs underwent placement of stents coated with high molecular weight PLLA-dexamethasone for assessment of arterial tissue and serum concentrations of dexamethasone at 1 h and 1, 2, 10 and 28 days after stent implantation.
Results: In vitro dexamethasone release occurred over the first 6 days. Stents coated with low molecular weight PLLA produced an intense inflammatory neointimal response. Stents utilizing the high molecular weight PLLA were well tolerated within the coronary vessel during the 28-day experiment. However, dexamethasone did not decrease neointimal hyperplasia. Dexamethasone concentrations in the arterial tissue were approximately 300,000-fold higher than those in the serum 24 h after stent implantation, remaining approximately 3,000-fold higher at 28 days.
Conclusions: The eluting stent utilizing high molecular weight PLLA appeared to be a well tolerated and effective means of providing sustained, site-specific drug delivery to the porcine coronary artery wall for at least 28 days.