Multi-functional lipopeptide micelles as a vehicle for curcumin delivery

Spherical micelles of ∼50 nm were self-assembled from an amphiphilic lipopeptide (C18H5R7RGDS, LP) containing H5R7RGDS heads and stearic acid (C18) tails for enhancing anti-tumor activity and efficient delivery of CUR. LP micelles significantly improved the aqueous solubility of CUR by 5400 times more than that of free CUR. In the case of pH 5.0, the electrostatic repulsion interaction among the ionized H5 fraction destroyed the structure of micelles, leading to significantly accelerated CUR release behavior. Hemolysis assay and proliferation inhibition test of normal cells confirmed apparently the excellent biocompatibility of LP. CUR-loaded LP micelles showed much higher cell inhibition on HepG2 cells and lower cytotoxicity on L02 cells than free CUR. With integrin-targeting sequence (RGD) and cell penetrating peptide (R8), the CUR-loaded micelles can more specifically and efficiently deliver CUR into integrin-overexpressed HepG2 cells than C18KR8 (LP-R1) and C18KRGDS (LP-R2) micelles. Combined with the enhanced drug solubility, distinctive pH-sensitive property and good tumor targeting, such LP micelles may have the clinical potential for tumor-targeting delivery.