Bivalirudin and sirolimus co-eluting coronary stent: Potential strategy for the prevention of stent thrombosis and restenosis

Abstract

Localized drug delivery with sustained elution characteristics from nanocarrier coated stents represents a viable therapeutic approach to circumvent concerns related to coronary stent therapy. We fabricated a Sirolimus (SRL) and Bivalirudin (BIV) releasing nanoparticles (NPs) coated stent for concurrent mitigation of vascular restenosis and acute stent thrombosis. SRL NPs were prepared by nanoprecipitation method whereas the BIV vesicles were generated using hydrophobic ion pair approach followed by micellization phenomenon. MTT assay and confocal microscopic analysis indicated superior anti-proliferative activity and higher cellular uptake of SRL NPs into human coronary artery smooth muscle cells, respectively. DSC and ATR-FTIR techniques confirmed the formation of complex between BIV and phosphatidylglycerol via some weak physical interactions. More than 2 fold rise in log P value was obtained for DSPG-BIV at 3:1 M ratio compared with native BIV solution. The SAXS analysis indicated formation of oligolamellar vesicles of DSPG-BIV complex which was preferentially entrapped into lipophilic lamellae of vesicles. APTT, PT, and TT tests revealed that the BIV vesicles caused significant prolongation of clotting time compared to native BIV solution. The SEM analysis showed uniform and defect free stent coating. In vitro release study demonstrated that SRL and BIV were eluted in a sustained manner from coated stents.