Investigation of novel sorafenib tosylate loaded biomaterial based nano-cochleates dispersion system for treatment of hepatocellular carcinoma

Sorafenib tosylate (ST), a European Medicines Agency (EMEA) and the U.S. Food and Drug Administration (FDA) approved orally active anticancer drug for liver cancer therapy. However, ST shows low oral bioavailability and therapeutic efficacy due to poor solubility, first-pass metabolism and narrow therapeutic window. Nano-cochleates are lipid constructed supramolecular congregations constituted of a negatively charged phospholipid with a divalent cation having potential targeting efficiency to cancer cells. In the present, we investigated the ST loaded nano-cochleates (STNCs) compressing 1,2-dioleoyl-sn-glycero-3-phospho-L-serine sodium salt (DOPS-Na) and cholesterol to increase ST oral bioavailability and therapeutic efficacy with low toxicity. The optimized STNCs showed entrapment efficiency, particle size and zeta potential of 85.55 +/- 2.46%, 470 +/- 23 nm, and -44.5 +/- 6.58 mV, respectively. The STNCs demonstrated 2.18 fold improvement in oral bioavailability with 3.21 and 2.29 fold decrease in half-life and mean residence time as well as 2.12 fold enhancement in-vitro cell viability as compared to ST alone. STNCs reversed the tumor formation in diethylnitrosamine (DEN)-induced rat hepatocellular carcinoma (HCC) which was reflected in the histopathological study. Further, antioxidant parameters, liver function tests, and hematological analysis revealed that STNCs had a pronounced effect on liver cancer. The nano-cochleates can stand out as a technology to facilitate the administration of ST in the clinical setting.

Automated summary

The study demonstrates that nano-cochleates can significantly improve the oral bioavailability and therapeutic efficacy of ST with low toxicity. The optimized STNCs show high entrapment efficiency and suitable particle size and zeta potential, resulting in a 2.18 fold improvement in oral bioavailability compared to ST alone, as well as significant reductions in half-life and mean residence time. This novel technology has promising potential for enhancing the administration of ST in clinical settings.