In vitro and in vivo performance of a dual drug-eluting stent (DDES)

Abstract

This study reports on a dual drug-eluting stent (DDES) that has an anti-proliferative and an anti-thrombotic in a biodegradable polymer-coated onto a cobalt-chromium stent. The DDES was prepared by spray coating the bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The 2-layered dual-drug coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. The in vitro anti-platelet behavior of the triflusal-loaded films was investigated by using dynamic platelet adhesion measurements. Additionally, the in vitro degradation and release study of the films and the stents w/single sirolimus and dual sirolimus-triflusal in different formulations were examined. Finally, in vivo studies (in a porcine carotid artery model) were performed for acute thrombosis, inflammation and restenosis at 30 days. The in vitro results show DDES can sustain release both anti-proliferation drug (sirolimus) and anti-thrombosis drug (triflusal), two drugs were controlled in different rates to effectively reduce thrombosis and proliferation at the same time. In vivo results show a significant reduction in restenosis with dual-drug eluting stent compared with the controls (a bare metal stent, a sirolimus coated and a pure polymer-coated stent). The reduction in restenosis with a dual sirolimus-triflusal eluting stent is associated with an inhibition of inflammation, especially thrombus formation, suggesting that such dual-drug eluting stents have a role to play for the treatment of coronary artery disease.