Development of RGD-Functionalized PEG-PLA Micelles for Delivery of Curcumin.

Curcumin (Cur), a hydrophobic polyphenolic compound, possesses a wide range of biological activities. However, its prominent application in cancer treatment is limited due to low aqueous solubility and rapid metabolism. Recently, micelle-based drug delivery system has been proven to be an attractive alternative for poorly soluble drugs. In order to improve the application of Cur as an anti-cancer agent, in this study, we synthesized the αvß3 integrin-targeted peptide (RGD) functionalized polymer (RGD-PEG-PLA). The RGD conjugated Cur loaded micelles (Cur-RPP) were prepared using the thin-film hydration method with modification and the preparation process was optimized with a central composite design. The obtained Cur-RPP presented spherical shape with a particle size of 20 nm and high drug loading (4.70%). Compared with the Cur propylene glycol solution, the in vitro release of Cur from the prepared micelles showed the sustained-release property. Cellular uptake of Cur-RPP was found to be higher than that of non-RGD modified micelles due to the binding effect between αvß3 integrin and RGD in human umbilical vein endothelial cells (HUVEC) and mouse melanoma cell lines (B16). In B16 tumor-bearing mice, Cur-RPP showed the stronger inhibiting effect on growth of tumor compared with non-RGD modified micelles. It could be concluded from these results that the RGD modified micelles might be a potential carrier for Cur.

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-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (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-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, 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.

Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in vitro characterization.

In this study, curcumin (Cur) loaded mixed micelles (Cur-PF), composed of Pluronic P123 (P123) and Pluronic F68 (F68), was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). The average size of the mixed micelles was 68.2 nm, and the encapsulating efficiency for Cur was 86.93%, and 6.996% for drug-loading. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-PF presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC(50) values on MCF-7 cells for Cur-PF and free Cur in DMSO solution were 5.04 µg/mL and 8.35 µg/mL, while 2.52 µg/mL and 8.27 µg/mL on MCF-7/ADR cells. It could be concluded from the results that P123/F68 mixed micelles might serve as a potential nanocarrier to improve the solubility and biological activity of Cur.