Synergistic effect of resveratrol and quercetin released from drug-eluting polymer coatings for endovascular devices

This study describes the development and evaluation of novel polymer films that provide controlled release of two vascular-protective polyphenols for endovascular devices. Resveratrol (RESV) and quercetin (QUER) have antimigratory and antiproliferative actions on vascular smooth muscle cells (VSMCs), inhibit both platelet and inflammatory cell activation, and promote endothelial cell function. Our aim is to develop and characterize coatings that release these drugs within a therapeutic range. The most synergistic drug combination, as determined by isobolographic analysis, was incorporated into an arborescent poly(styrene-isobutylene-styrene) tri-block polymer (arbIBS) and applied to stainless steel coupons using an electrospray process. Physical characterization of the resulting coating revealed a film featuring micro-scale architecture consisting of drug-containing domains. To determine drug-mediated effects, vascular cells were exposed to coatings incorporating several loadings of RESV and QUER. Results from this study indicate that arbIBS exhibits no cytotoxicity, and that the films release RESV and QUER at therapeutic levels, dose-dependently inhibiting macrophage activation, VSMC proliferation, and platelet stimulation. We conclude that RESV and QUER released from arbIBS interfere with key processes responsible for in-stent stenosis, suggesting that RESV and QUER may have utility as therapeutics in a novel coating for device-based interventions.