Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization

J Control Release. 2012 Apr 10;159(1):27-33. doi: 10.1016/j.jconrel.2012.01.008. Epub 2012 Jan 17.

Abstract

Late-term thrombosis associated with drug-eluting stents may be due to the non-selective actions of antimitogenic drugs on endothelial cells, leading to delayed vascular healing after stenting angioplasty. Currently, there is a need for stent-based therapies that can both attenuate neointimal hyperplasia and promote re-endothelialization. The aim of this study was to compare the effects of a resveratrol (R)- and quercetin (Q)-eluting stent with that of a bare metal stent (BMS) on neointimal hyperplasia and re-endothelialization in a rat model of arterial angioplasty and stenting. Miniature stents (2.5×1.25mm) were sprayed with nanocomposite coatings containing two concentrations of R:Q (50:25μg/cm(2) (RQ1) or 150:75μg/cm(2) (RQ2)). The stents were deployed into the common carotid artery of rats and their impact on vascular remodeling was compared to that of BMS. Luminal stenosis in arteries stented with RQ2-eluting stents was reduced by 64.6% (p<0.05) compared to arteries stented with BMS. Accompanying this effect was a 59.8% reduction in macrophage infiltration (p<0.05). There were no differences found between RQ1 and BMS. Finally, the RQ2-coated stent accelerated re-endothelialization by 50% compared with BMS (p<0.05). Thus, compared with BMS, local delivery of R and Q from a stent platform significantly reduced in-stent stenosis, while promoting re-endothelialization. These data suggest that R and Q may be favorable candidates for novel stent coatings, potentially reducing the risk of late thrombosis associated with drug-eluting stents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty
  • Animals
  • Antimitotic Agents / administration & dosage*
  • Cell Proliferation / drug effects
  • Constriction, Pathologic / drug therapy
  • Drug-Eluting Stents*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Female
  • Hyperplasia / drug therapy
  • Hyperplasia / pathology
  • Male
  • Nanocomposites
  • Neointima / drug therapy
  • Neointima / pathology
  • Quercetin / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / administration & dosage*

Substances

  • Antimitotic Agents
  • Stilbenes
  • Quercetin
  • Resveratrol