Nanoparticles of a biodegradable polymers for clinical administration of paclitaxel

Abstract

Paclitaxel, one of the most potent chemotherapeutic agents, is successfully applied in clinical known as an injection formulation, TaxolA?. However, the excipient Cremophor EL causes many side effects. Nanoparticles of biodegradable polymers provide an ideal solution. Conventional nanoparticles, unfortunately, suffer from short circulation due to their recognition and capture by the RES (reticuloendothelial system). We prepared stealth (PEGylated) nanoparticles from the synthesized methoxy poly(ethylene glycol)-co-poly(D,L-lactide) (MPEG-PLA) or their blends with poly(D,L-lactide) (PLA) by the nanoprecipitation method. < 100 nm nanoparticles with abundant PEG surface density were obtained. Effects of fabrication parameters on the particle size and drug encapsulation efficiency were detailed. Pharmacokinetic studies with SD rats showed that paclitaxel loaded in MPEG-PLA nanoparticles had a much higher AUC (area under curve) than conventional nanoparticles and TaxolA?, suggesting the prolonged circulation of MPEG-PLA nanoparticles. Nanoparticles also offer a platform to oral chemotherapy of paclitaxel, which has very low oral bioavailability. We prepared bioadhesive nanoparticles, i.e., chitosan-coated or montmorillonite (MMT) incorporated poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles to enhance the absorption and affinity to the intestinal mucus/epithelium, which was demonstrated by their enhanced uptake in Caco-2 and HT-29 cells in vitro.