title: 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.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.forename: Freddy Y C
authors.initials: FY
authors.lastname: Boey
authors.forename: Eeva M
authors.initials: EM
authors.lastname: Lahti
authors.forename: P R
authors.initials: PR
authors.lastname: Umashankar
authors.forename: Mira
authors.initials: M
authors.lastname: Mohanty
authors.forename: Sabareeswaran
authors.initials: S
authors.lastname: Arumugam
authors.forename: Laxmikant
authors.initials: L
authors.lastname: Khanolkar
authors.forename: Sudhir
authors.initials: S
authors.lastname: Vaishnav
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D054855:Drug-Eluting Stents; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy*; D008422:Materials Testing; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020123:Sirolimus / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013499:Surface Properties; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D020099:Coated Materials, Biocompatible; D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D020123:Sirolimus