Curcumin loaded polymeric micelles of variable hydrophobic lengths by RAFT polymerization: Preparation and in-vitro characterization

Curcumin is a prominent natural anticancer drug candidate accompanied by major limitations such as remarkable hydrophobicity, instability, and poor bioavailability. In the present study, polymeric micelle encapsulation was addressed to improve the solubility and stability of curcumin. Methoxy poly (ethylene glycol)-bpoly (methyl methacrylate) (mPEG-b-PMMA) amphiphilic block copolymers with variable hydrophobic lengths were synthesized using the reversible addition-fragmentation chain transfer (RAFT) polymerization method. Block copolymers can be effectively self-assembled in the aqueous medium due to their amphiphilic nature giving rise to micellar nanoparticles. The assembly of the copolymers was evaluated in terms of critical micelle concentration (CMC) and particle size distribution, which indicated a very low CMC value. Afterward, curcumin was successfully loaded into the mPEG-b-PMMA micelles resulting in a significant 400-fold solubility enhancement. Moreover, the cytotoxicity assay revealed that curcumin-loaded mPEG-b-PMMA micelles notably inhibited the growth of SW-48 colorectal cancer cells, A2780 ovarian carcinoma cells, and HepG2 human hepatoma cells in a dose-dependent manner. The free radical scavenging activity of curcumin-loaded mPEG-b-PMMA micelles demonstrated that the encapsulation of curcumin led to greater stability, particularly in alkaline pH. Taking all together, the results suggest that mPEG-b-PMMA micelles, prepared at optimum hydrophobic length, can serve as a promising nanocarrier system in curcumin delivery.