Preparation of nanoparticles consisted of poly( l-lactide)–poly(ethylene glycol)–poly( l-lactide) and their evaluation in vitro

Abstract

This study describes the preparation and the evaluation of biodegradable poly( l-lactide)–poly(ethylene glycol)–poly( l-lactide) copolymer (PLA–PEG–PLA) nanoparticles containing progesterone as a model drug. PLA and PLA–PEG–PLA copolymers, whose PEG content ranged from 5.2 to 25.8% (w/w), were polymerized in our laboratory. PEG with weight-average molecular weight (Mw) 6600 or 20 000 was introduced as a hydrophilic segment into a hydrophobic PLA homopolymer. A solvent evaporation method was used to prepare the nanoparticles. The drug trapping efficiencies were around 70% and the weight-averaged mean diameters of the nanoparticles were less than 335 nm. The amount of drug released increased as the PEG content and Mw of PLA–PEG–PLA copolymers increased and the total Mw of copolymers of nanoparticles decreased. The initial burst of drug release was reduced by removing the low Mw fraction from the polymer. During the release test, both the extent to which the copolymers were degraded and the size of the nanoparticles were increased slightly by increasing the content of PEG in the polymers. Drug release from the nanoparticles could potentially be controlled by changing the PEG content, PEG Mw and total Mw of the copolymer. The molecular weight distribution (Mw/Mn, Mn: number-average molecular weight) of copolymers was also an important factor for controlled release.