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

  作者 Kleinedler, JJ; Foley, JD; Orchard, EA; Dugas, TR  
  选自 期刊  Journal of controlled release;  卷期  2012年159-1;  页码  27-33  
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[摘要]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 (2.5x1.25 mm) were sprayed with nanocomposite coatings containing two concentrations of R:Q (50:25 mu g/cm(2) (RQ1) or 150: 75 mu g/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. (C) 2012 Elsevier B.V. All rights reserved.

 
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