Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting

Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG(3000)-PIA(2000), was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG(2000)-PLA(2000) (Cur-PPs) or mPEG(2000)-PLA(2000) and Folate-PEG(3000)-PLA(2000) (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG(3000)-PLA(2000) and mPEG(2000)-PLA(2000) at 1:9. The average size of the mixed micelles was 70 nm, the encapsulating efficiency and drug-loading were 80.73 +/- 0.16% and 4.84 +/- 0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.