Pluronic modified PLA based hybrid block copolymeric nanoformulation enhanced anti-cancer therapeutic efficacy of Epirubicin

Epirubicin is widely used anthracycline to treat various human malignancies. However, dose limiting therapeutic efficacy, cardiac toxicity, and drug resistance are major concerns associated with the Epirubicin treatment for cancer therapy. In the present study, we synthesized a series of novel Pluronic (R) modified PLA based hybrid block copolymers comprising PLA-PEG-PPG-PEG-PLA and mPEG-PLA block copolymers. Nanoparticles prepared with these block copolymers were evaluated for the encapsulation of Epirubicin with an aim to reduce its toxicity and enhance anti-cancer therapeutic efficacy. Epi-NPs were showed an average diameter of 102 +/- 3 nm, and encapsulation efficiency of 94 +/- 2 %. The in-vitro drug release profile of Epi-NPs exhibited slow and sustained release in PBS (pH-7.4). In-vitro cytotoxicity studies of Epi-NPs demonstrated the efficient growth inhibition of breast cancer cell lines. Twice a week treatment of EAC syngeneic breast cancer tumor bearing Balb/c mice with commercially available Epirubicin and Epi-NPs at a dose of 3 mg/kg showed tumor growth inhibition of -62 % and -80%, respectively. In contrast, the 6 mg/kg dosing of Epi-NPs resulted in complete tumor eradication. These findings demonstrate that the synthesized Pluronic (R) modified PLA based block copolymer NPs can effi-ciently deliver Epirubicin with enhanced therapeutic efficacy and reduced toxicity.