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 αvβ3 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 αvβ3 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.