Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries

Aim: the use of currently marketed drug-eluting stents (des) presents safety concerns,including an increased risk for late thrombosis in the range of 0.6% per year in patients,including acute coronary syndrome,which is thought to result from delayed endothelial healing effects. a new des system targeting vascular smooth muscle cells without adverse effects on endothelial cells is therefore needed. platelet-derived growth factor (pdgf) plays a central role in the pathogenesis of restenosis; therefore,we hypothesized that imatinib mesylate (pdgf receptor tyrosine kinase inhibitor) encapsulated bioabsorbable polymeric nanoparticle (np)-eluting stent attenuates in-stent neointima formation. methods: effects of imatinib-incorporated np-eluting stent on neointima formation and endothelial healing were examined in a pig coronary artery stent model. effects of imatinib-np were also examined in cultured cells. results: in a cultured cell study,imatinib-np attenuated the proliferation of vascular smooth muscle cells associated with inhibition of the target molecule (phosphorylation of pdgf receptor-β),but showed no effect on endothelial proliferation. in a pig coronary artery stent model,imatinib-npeluting stent markedly attenuated in-stent neointima formation and stenosis by approximately 50% as assessed by angiographic,histopathological,and intravascular ultrasound imaging analyses. imatinib- np-eluting stent also attenuated map kinase activity,but did not affect inflammation and re-endothelialization. conclusion: these data suggest that suppression of neointima formation by a imatinib-np-eluting stent holds promise as a molecular-targeting np delivery system for preventing in-stent restenosis.