| The development of biodegradable nanoparticles as drug delivery vehicles presents an improved avenue for intracellular targeted drug delivery. Biodegradable nanoparticles have demonstrated an ability to provide controllable, sustained drug release in vitro. However, in vivo studies have shown that nanoparticles are not effective at adhering to vascular walls under shear stress. The purpose of this study was to investigate methods to improve cellular uptake and targeting of nanoparticles in activated or inflamed endothelial cells (ECs) under fluid shear stress and to determine whether the material properties of a biodegradable polymer, poly (lactic-co-glycolic) acid (PLGA), affected cellular uptake. The hypothesis for this project was that by mimicking the binding of platelets with activated ECs (glycoprotein Ibalpha (GP Ibalpha)-P-selectin), GP Ibalpha-conjugated nanoparticles could exhibit increased targeting and higher cellular uptake in injured or activated endothelial cells under physiological flow conditions. (Abstract shortened by UMI.)... |
