Polymeric micelles for parenteral delivery of curcumin: Preparation, characterization and in vitro evaluation

摘要

Amphiphilic methoxypoly(ethylene glycol)-b-poly(e{open}-caprolactone-co-p-dioxanone) [MPEG-P(CL-co-PDO)] copolymers were synthesized and characterized by 1H NMR and gel permeation chromatography (GPC). The influence of copolymer compositions on the crystallinity, water solubility, and hydrolytic degradation rate of the copolymers was investigated. Curcumin, a potential anticancer drug with poor water solubility, was successfully loaded into the MPEG-P(CL-co-PDO) micelles by a solid dispersion method with a high encapsulation efficiency (>95%). The curcumin-loaded micelles were monodisperse (PDI<0.15) with small particle sizes (around 30nm) and were easy to reconstitute in water (just by manual shaking) after lyophilization. The stability of the reconstituted micelles at the room temperature depended on the curcumin loading contents and the PDO/CL ratios in the copolymers. XRD patterns revealed that curcumin was molecularly dispersed in the copolymer micelles. In vitro drug release test results showed that curcumin was slowly released from the micelles without any burst effect. The cytotoxicity assay indicated that curcumin-loaded MPEG-P(CL-co-PDO) micelles markedly inhibited the growth of PC-3 human prostate cancer cells in a dose-dependent manner. These results suggested that MPEG-P(CL-co-PDO) micelles would be a promising carrier for delivery of curcumin.