Copolymeric Micelles Loading Curcumin: Preparation, Characterization and In Vitro Evaluation.

Abstract

Curcumin (Cur) has potent antitumor activity; however, its clinical use is limited due to its hydrophobicity and instability at physiological pH. In this work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur-loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having excellent water-solubility and good stability at pH 7.4. The freeze-drying powders of the Cur-loaded micelles were easily rehydrated. It was found that Cur was slowly released from the micelles with a cumulative drug release percentage of 78.11% within 14 days and there was no obvious drug burst release. MTT tests showed that, the IC50 values of the Cur-loaded micelles were lower than those of free Cur against cancer cells (MDA-MB-231 cells and 4T1 cells). No matter for cancer cells (MDA-MB-231 cells and 4T1 cells) or healthy cells (L929 cells), cell viabilities were all >90% after incubating with the blank MPEG2K-P(CL-co-LLA) micelles, even at very high micelle concentration (up to 1000 μg/mL), indicating the blank micelles were of no or extremely low cytotoxicity per se. The Cur-loaded micelles were taken up mainly via endocytosis route and the cellular uptake on 4T1 cells increased with incubation time. They could induce more cell apoptosis compared to free Cur. These results suggested that curcumin-loaded MPEG2K-P(CL-co-LLA) micelles may be a potential nanoscale drug delivery system for cancer therapy.