Drug-eluting stents have been widely used in the treatment of coronary heart diseases, but the long-term efficacy has been dependent on the control of drug release kinetics. Though evenly distributed release with minimal burst release is much desired for the antiproliferative drugs used on stents, strategies for sustained zero-order release have not been specifically identified. We investigated vapor-based fabrication of polymer nanocoatings for the encapsulation of antiproliferative drugs. Drug release kinetics was regulated by adjusting the composition and thickness of the nanocoatings. Zero-order release of atorvastatin and sirolimus for 30 days was achieved using a poly(2-dimethylamino ethyl methacrylate-co-ethylene glycol diacrylate) (PDE) nanocoating with a monomer/cross-linker molar ratio of 0.78. The drug release rate was modulated using drug dose and coating thickness. The combination of coating surface and drug release suppressed the viability and proliferation of human coronary artery smooth muscle cells to below 57% at dose density as low as 10 μg/cm2. The PDE nanocoatings also reduced surface platelet adhesion without detrimental effect on red blood cells. The findings of this study demonstrate the potential of applying vapor-deposited polymer nanocoatings in modulating the release kinetics and thus improving the therapeutic efficacy of drug-eluting stents.
Keywords: antiproliferative drugs; controlled release; platelet adhesion; polymer nanocoatings; vapor deposition; zero-order.