Antithrombogenic coating of stents using a biodegradable drug delivery technology

To reduce the thrombogenic properties of coronary artery stents, a biodegra dable polylactic acid (PLA) stent coating with an incorporated thrombin inh ibitor and a platelet aggregation inhibitor has been developed. In an ex vi vo human stasis model, its effect on platelets, plasmatic coagulation and i ts release characteristics were studied using whole blood. Bare steel and b are gold-surface stents were compared to steel and gold-surface stents coat ed with PLA (30 kDa) containing 5% polyethyleneglycol (PEG)-hirudin and 1% iloprost, with an empty tube as control. Markers of activated coagulation ( prothrombin fragment F1-2 and thrombin-antithrombin III complex, TAT), were assayed and the release of drugs from the coating was assessed by aPTT and collagen-induced platelet aggregation. Bare steel and gold stents were com pletely covered by a blood clot, and high levels of coagulation markers (F1 -2 fragment and TAT) were detected, No differences in the thrombogenic prop erties were found between bare gold or steel stents. Coated stents were fre e of blood clots and only minor elevations of markers were detected. Releas e data from in-vitro studies over 90 days showed a gradual release of the d rugs with an initial exponential release characteristic for PEG-hirudin, sl ow release of iloprost and a 10% degradation of the PLA carrier. This drug releasing biodegradable coating effectively reduced thrombus formation inde pendent of the metallic surface.