Core/Shell Polymer Nanoparticles Encapsulated With P38 Mapk Inhibitor For Targeted Drug Delivery

Nanoparticles as carriers offer a promise in specifically delivering therapeutics to desired locations in human bodies and dramatically enhancing therapeutic effects, but problems have arisen in the rational design of nanoparticles currently used. Hybridized lipid/polymer nanoparticles provide flexible designs, improved circulation time and targeted delivery. The project utilized these novel properties of hybridized lipid/polymer nanoparticles to specifically deliver anti-inflammatory drug to inflamed vasculature. 1) We designed core-shell polymer nanoparticles, consisting of a PLGA polymer core surrounded by a soy lecithin lipid monolayer and a DSPE-PEG polyethylene glycol corona, where carboxyl functional groups may be attached for bioconjugation. We successfully made homogeneous nanoparticles, averaged 100nm in diameter, noticing the nanoparticle size being strongly dependent on the ratios and amounts of the nanoparticle components. We determined the nanoparticle sizes using dynamic light scattering and scanning electron microscope and found the best conditions for reproducible 100 nm-sized nanoparticles. 2) To image these nanoparticles in cells, we encapsulated fluorescent dyes (R6G and Cy5). 3) Activation of the endothelium recruiting neutrophils during acute lung injury might be a central target to deliver therapeutics to regulate the adhesive molecules on the endothelium, strongly governed by MAPK pathway. We incorporated a water-insoluble p38 MAPK inhibitor, SB202190 and measured drug incorporation efficiency in nanoparticles using High-Pressure Liquid Chromatography. 4) To specifically deliver therapeutic nanoparticles to inflammatory endothelial cells, anti-VCAM-1 antibodies are conjugated to the nanoparticle’s surface using carboxyl-amine reaction. Continuing research includes evaluating the therapeutic effect and targeted delivery of these hybridized lipid/polymer nanoparticles in acute lung injury.