Intramural α v β 3 ‐ Targeted Rapamycine Nanoparticles after Angioplasty Reduces Stenosis Without Delaying Intimal Healing

Abstract

Drug eluting stents have demonstrated the anti-restenotic benefit of local antiproliferative drug delivery following angioplasty, but delayed re-endothelialization creates a risk of thrombosis for up to 30 months. We have shown that intramural αvβ3- targeted rapamycin nanoparticles can reduce arterial stenosis after angioplasty. The objective of this study was to determine whether intramural αvβ3-targeted rapamycin nanoparticles impair intima endothelial repair. Femoral arteries of NZW rabbits fed an atherogenic diet for 3 months were subjected to balloon stretch injury. αvβ3-intergrin targeted perfluorocarbon nanoparticles with 0.3-mol% rapamycin in the surfactant were locally infused into one artery while the contralateral artery received saline or αvβ3-targeted nanoparticles without rapamycin as controls. Microscopic morphometric analysis following Carstair’s staining showed that endothelial recovery following rapamycin treatment was not prolonged when compared with control at all time points (Figure 1). Intimal plaque area observed en face was significantly smaller (P<0.05) in arteries exposed to rapamycin nanoparticles than that in controls (Figure 2). In conclusion, constrained intramural delivery of rapamycin using αvβ3- nanoparticles immediately after balloon angioplasty diminishes acute plaque formation without impairing endothelial healing. Figure 1Open in figure viewerPowerPoint Figure 2Open in figure viewerPowerPoint