Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model

Aim: the use of currently marketed drug-eluting stents presents safety concerns including increased late thrombosis,which is thought to result mainly from delayed endothelial healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). we recently developed a bioabsorbable polymeric nanoparticle (np)-eluting stent using a novel cationic electrodeposition technology. statins are known to inhibit the proliferation of vascular smooth muscle cells (vsmc) and to promote vascular healing. we therefore hypothesized that statin-incorporated npeluting stents would attenuate in-stent stenosis without delayed endothelial healing effects. methods: among six marketed statins,pitavastatin (pitava) was found to have the most potent effects on vsmc proliferation and endothelial regeneration in vitro. we thus formulated a pitava-np-eluting stent (20 μg pitava per stent). results: in a pig coronary artery model,pitava-np-eluting stents attenuated in-stent stenosis as effectively as polymer-coated sirolimus-eluting stents (ses). at ses sites,delayed endothelial healing effects were noted,whereas no such effects were observed in pitava-np-eluting stent sites. conclusion: pitava-np-eluting stents attenuated in-stent stenosis as effectively as ses without the delayed endothelial healing effects of ses in a porcine coronary artery model. this nanotechnology platform could be developed into a safer and more effective device in the future.