Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating.

Abstract

The pleiotropic effects of the atorvastatin-fenofibrate combination can be effectively harnessed for site-specific therapy to minimize stent-related complications. The present study aims to utilize the pleiotropic effects of these two drugs entrapped in a uniform and defect-free coating of poly(l-lactide-co-caprolactone) (PLCL) on a stainless steel stent to overcome stent-associated limitations. The stent coating parameters were optimized using ultrasonic spray coating technique to achieve a thin, smooth, and defect-free dual drug-loaded polymer coating on the stent. The dual drug-loaded polymer coated stent was characterized for surface morphology, thickness and coating integrity. In vitro drug release kinetics of the fabricated stent reveals a sustained release of both drugs for more than 60 days. Significant reduction of thrombus formation and adhesion of lipopolysaccharide-stimulated macrophages on the dual drug containing polymer-coated stent indicates that the drug combination possesses antithrombotic and anti-inflammatory effects. The combination did not adversely influence endothelialization but significantly retarded smooth muscle cell proliferation indicating its potential to overcome restenosis. No bacterial biofilm formation was observed on the stent due to the antibacterial activity of atorvastatin. A rat subcutaneous model was used to evaluate the biocompatibility of the coated stent and compared with the commercial stent. MicroCT, scanning electron microscopy, and morphometric analyses revealed that the coated stents exhibited excellent histocompatibility with no inflammatory response as evidenced from the cytokine levels measured 28 days postimplantation. Our data demonstrates for the first time that the combination of atorvastatin and fenofibrate can be successfully employed in cardiovascular stents to overcome the current limitations of conventional drug-eluting stents.