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

Abstract

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.

Polyurethane–polylactide-based material doped with resveratrol decreases senescence and oxidative stress of adipose-derived mesenchymal stromal stem cell (ASCs)

“…The study conducted by Kleinedler et al 24 describes the development and evaluation of polymers that provide a release of vascular-protective polyphenols for endovascular devices. RES combined with querencin was incorporated into an arborescent poly(styrene-isobutylene-styrene) tri-block polymer (arbIBS) and applied to stainless steel coupons using an electrospray process.…”

Are sirtuins viable targets for improving healthspan and lifespan?

“…Other cardioprotective effects of resveratrol include inhibition of vascular smooth muscle cell proliferation 152,153 , which has therapeutic relevance for the treatment and/or prevention of pulmonary hypertension 131 and neointima formation 129 . On the basis of the synergistic inhibitory effects of resveratrol on vascular smooth muscle cell proliferation, macrophage activation and platelet stimulation, the use of resveratrol-eluting coatings for the prevention of in-stent stenosis is being considered 154 .…”

Synergy Study of the Inhibitory Potential of Red Wine Polyphenols on Vascular Smooth Muscle Cell Proliferation

“…To combat restenosis, for example, compounds inhibiting VSMC proliferation are of interest for local application in drug-eluting stents, and the usage of combinations of synergistically interacting components might lead to a superior treatment outcome. Another study further demonstrating the potential of such a synergistic treatment approach has been recently performed with a combined resveratrol and quercetin formulation incorporated into drug-eluting polymer coatings with possible future application in the prevention of in-stent restenosis [35].…”