Preparation of DHAQ-loaded mPEG-PLGA-mPEG nanoparticles and evaluation of drug release behaviors in vitro/in vivo

摘要

This study describes the preparation and the evaluation of biodegradation monomethoxy (polyethylene glycol)-poly (lactide-co-glycolide)-monomethoxy (polyethyleneglycol) (mPEG-PLGA-mPEG, PELGE) nanoparticles (PELGE-NP) containing mitoxantrone (DHAQ) as a model drug. PELGE copolymers with various molar ratios of lactic to glycolic acid and different molecular weights and various content mPEG were synthesized by ring-opening polymerization. mPEG with weight-average molecular weight (Mw) 2000 or 5000 was introduced as a hydrophilic segment into a hydrophobic PLGA. A double emulsion method with dextran70 as stabilizer in the external aqueous phase was used to prepare the nanoparticles. The drug entrapment efficiencies were more than 80% and the mean diameters of the nanoparticles were less than 200 nm. Various PELGE was studied as biodegradable drug carriers and there in vitro/in vivo release profiles were examined. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vitro/in vivo release properties. The amount of drug released increased as the mPEG contents increased and the molar ratios of lactic acid decreased in vitro. The intravenous (i.v.) administration of mPEG-PLGA-mPEG nanoparticles of DHAQ in mice resulted in prolonged DHAQ residence in systemic blood circulation compared to the intravenous administration of PLGA nanoparticles.