Abstract
Curcumin is a natural compound widely used in various therapies, and it has been considered a potential anticancer agent recently. Nevertheless, the clinical application of curcumin is hindered due to its poor water solubility. Mixed micelles as a curcumin encapsulating carrier was developed composed of mPEG5000-PSA (methoxy poly(ethylene glycol-b-sebacic anhydride)) and mPEG2000-PLLA (methoxy poly(ethylene glycol-b-L-lactic acid)). The formation of mixed micelles was prepared by a solvent evaporation method. The character of mixed micelles was measured by 1H-NMR, dynamic light scattering (DLS) and confocal laser scanning microscope. Mixed micelles showed good stability in PBS buffer solution (pH=7.4) during 24 days whereas the average size of micelles of mPEG5000-PSA was greater than 200 nm in 2 days. The size of Curcumin-loaded mixed micelles increased with increasing curcumin loading. Encapsulation efficiency of curcumin of mixed micelles presented high level loading (E.E=78%). The water solubility of curcumin was increased to 0.16 mg/ml due to mixed micelles (267 fold increase compared with original solubility of curcumin, 0.6 μg/ml)。The study of drug release showed mixed micelles release curcumin gradually, while mPEG5000-PSA showed large initial burst. Cytotoxicity studies of curcumin-free micelles (mPEG5000-PSA and mPEG2000-PLLA) indicated low cytotoxicity. By contrast, a linear dependency of cytotoxicity was observed with treatment concentration of curcumin. The morphology of mixed micelles was core/shell-like as observed by TEM. In vivo studies showed curcumin-free micelles have no toxicity for rats. Finally, mixed micelles are good carriers suitable for controlled drug release system. Curcumin-loaded mixed micelles improve poor water solubility of curcumin dramatically and broaden its range of clinical applications.