Key result
Sustained intracoronary delivery of dexamethasone by a novel polymer-coated stent achieved 3,000-fold higher tissue concentrations at 28 days but did not decrease neointimal hyperplasia in pigs.
Why the study?
Development of techniques to provide sustained local drug delivery using polymer-coated stents for intracoronary drug delivery was needed to assess feasibility, safety, and efficacy.
Does sustained local delivery of dexamethasone via a polymer-coated eluting stent decrease neointimal hyperplasia in a porcine coronary injury model?
Does sustained local delivery of dexamethasone via a polymer-coated eluting stent decrease neointimal hyperplasia in a porcine coronary injury model?
A novel intravascular eluting stent utilizing high molecular weight PLLA provides sustained, site-specific delivery of dexamethasone to the porcine coronary artery wall for up to 28 days, though it does not reduce neointimal hyperplasia.
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.
No takes yet. Share an insight, caveat, or question.
Lincoff et al. (1997) studied Restenosis. Dexamethasone-eluting stent vs. Uncoated stents or PLLA-coated stents was evaluated on Neointimal thickness. Sustained intracoronary delivery of dexamethasone by a novel polymer-coated stent achieved 3,000-fold higher tissue concentrations at 28 days but did not decrease neointimal hyperplasia in pigs.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: