Abstract
Ellagic acid (EA) is an anticancer agent as evidenced in numerous pre-clinical studies. The clinical application of EA is limited because of its poor aqueous solubility and bioavailability. The present study was designed to formulate polymeric micelles of the drug using poly(L-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) di-block copolymer. The particle size and entrapment efficiency of EA by the polymeric micelle were found to be dependent on the concentration of polymer. Consequently, optimized micellar formulations with 82 +/- 7.1 nm size and 45.32 +/- 5.43% drug entrapment were further evaluated for cytotoxicity, cell cycle arrest, and apoptotic potential in the human lung adenocarcinoma cell line, A549. EA was toxic to A549 cells, and this cytotoxicity was significantly increased when EA was delivered using a micellar formulation. Flow cytometry analysis revealed a superior G1 phase arresting potential of the optimized EA-loaded PLGA-PEG micelles (PLGA-PEG-EA-F3), with a concomitant increased apoptotic potential. Further investigation of the mechanism of apoptosis showed a significant overexpression of caspase-3 in A549 cells when treated with PLGA-PEG-EA-F3 compared to free EA. Thus, it can be concluded that the PLGA-PEG polymeric micellar platform for EA could be a potential tool to treat lung cancer.