Enhanced therapeutic efficacy and cytotoxicity of doxorubicin-loaded vitamin E – Pluronic micelles against liver cancer

Abstract

In this study, a new polymeric micelle delivery system was developed to increase the therapeutic efficacy of doxorubicin (DOX) and to reduce its associated side effects. For this purpose, DOX-loaded Pluronic-alpha-tocopheryl succinate polymeric micelles (P/TOS-DOX) were successfully prepared for the therapeutic treatment of hepatocellular carcinoma. We show that the drug-loaded micelles exhibit typical pH-dependent and sustained drug release profile. These micelles were nanosized, around ∼100 nm, with spherical morphology. The micelles were predominantly distributed in the cytoplasmic region, which facilitates the cancer-killing potency of the chemotherapeutic drug. The IC₅₀ value of DOX and P/TOS-DOX remained at 1.18 μg ml⁻¹ and 0.72 μg ml⁻¹, respectively, indicating significant inhibition of cancer cell proliferation by the micellar carrier. Micellar incorporation of the drug effectively shielded it from elimination and subsequently prolonged the blood circulation and half-life of the anticancer drug. P/TOS-DOX accumulated preferentially in the tumor immediately after systemic administration, and a significant proportion of the drug was observed by the end of 24 h. Especially, P/TOS-DOX exhibited superior tumor growth inhibition compared to that in the free DOX-treated group. More importantly, the side effects of DOX were effectively decreased when it was administered using micellar carriers. Overall, our results suggest that P/TOS-DOX could be an attractive carrier in the therapeutic approach to hepatocellular carcinoma.