Nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-poly(D,L-lactide) blends for controlled release of paclitaxel

Abstract

Paclitaxel is one of the best antineoplastic drugs found in nature in the past decades, which has excellent therapeutic effects against a wide spectrum of cancers. Because of its high hydrophobicity, Cremophor EL has to be used as adjuvant in its clinical dosage form (Taxol®), which has been found to cause serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution. In this research, paclitaxel-loaded nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-polylactide (PLA/ MPEG-PLA) blends of various blend ratio 100/0, 75/25, 50/50, 25/75, and 0/100 were formulated by the nanoprecipitation method for controlled release of paclitaxel. It was found that increasing the proportion of MPEG-PLA component in the blend from O to 100% resulted in a progressive decrease of the particle size from 230.6 ± 11.1 nm to 74.8 ± 14.0 nm. The zeta potential of the drug-loaded nanoparticles was increased accordingly from -19.60 ± 1.13 mV to a nearly neutral, that is, -0.33 ± 0.28 mV, which indicates the gradual enrichment of PEG segments on the particle surface. The findings were further confirmed by X-Ray Photoelectron Spectroscopy (XPS) analysis. Differential scanning calorimetry (DSC) analysis showed that the glass transition temperature of PLA was significantly decreased from 58.7 to 52.1°C with an increase of MPEG-PLA proportion from 0 to 75%, suggesting the miscibility of PLA and MPEG-PLA. The pure PLA nanoparticles (100/0) exhibited the slowest drug-release rate with 37.3% encapsulated drug released from the nanoparticles for 14 days while the MPEG-PLA nanoparticles (0/100) achieved the fastest drug release with 95.9% drug release in the same period. © 2006 Wiley Periodicals, Inc.