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Abstract:
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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 Iba (GP Iba ) -P -selectin ) , GP Iba -conjugated nanoparticles could exhibit increased targeting and higher cellular uptake in injured or activated endothelial cells under physiological flow conditions . To test this hypothesis , carboxyl polystyrene nanoparticles loaded with green fluorescent dyes were selected as a model particle . Using confocal microscopy , the study found that conjugation of 100 nm polystyrene nanoparticles with GP Iba significantly increased cellular uptake and targeting under fluid shear stress . To develop therapeutic carriers , biodegradable nanoparticles were developed from PLGA using a standard double emulsion technique . Using microscopy , fluorescent measurement , and protein assays , similar cellular uptake properties were observed for 100 nm PLGA and polystyrene nanoparticles , suggesting that the uptake properties of these nanoparticles in ECs were not strongly affected by their material properties . The study also found that PLGA nanoparticles were able to provide sustained drug release for at least 14 days . Preliminary results from this project demonstrate that our novel platelet -mimicking nanoparticles may be the first step towards developing a targeted , sustained , drug delivery system , with the ability to overcome shear regulated cellular uptake . |