Doxorubicin and Curcumin Mediated Combinatorial Nanoparticulate Delivery System for Improvement of Chemotherapy Efficacy in Liver Cancer

摘要

The current research was carried out to evaluate curcumin (CUR) and Doxorubicin (DOX) mediated combinatorial therapy using PLGA nanoparticles in rat model. CUR-DOX nanoparticles were optimized by Box-Behnken statistical design. Size of optimized CUR-DOX loaded NPs determined by dynamic light scattering was 80.23 nm, while Zeta potential was 17.3 +/- 3.8 mV. The entrapment efficiencies (EE) for both active ingredients were found in the range of 86.98-97.23%. CUR and DOX were released in a sustained manner from NPs over the period of 50 h. The treatment efficacy and safety were evaluated based on tumor volume, body weight, and survival rate of rats. CUR-DOX Nps showed highest antiproliferative effect in HeLa [Chang-Liver] and HepG2 cells as compared to DOX loaded and CUR Nps. The cellular uptake efficiencies for CUR-DOX Nps were found to be time dependent and much higher than only DOX loaded and CUR loaded Nps on both cell lines. The CUR-DOX loaded Nps significantly maintained higher impeachment of CUR and DOX in liver tissues (approx. 9.5 mu g/g of liver). Moreover, the rats treated with CUR-DOX Nps showed 100% survival rate. Histopathology and immune histochemical study also displayed superior anticancer activity of the developed formulation. These results showed that the CUR-DOX Nps can play vital role in promoting liver cancer cell targeting and tumors in sustained and gradual manner, to improve therapeutic efficacy of CUR and DOX. The collective results demonstrate that combinatorial therapy of CUR-DOX loaded Nps in rat model is safe and effective in improvement of chemotherapy efficacy in liver cancer.