Preparation and characterization of dual drug containing carrier system for liver cancer treatment and In Vitro investigation of its effect on liver cancer

Liver cancer is the sixth most diagnosed cancer type and is the third leading cause of cancer-related deaths. Sorafenib is a drug used in the first-line treatment of hepatocellular carcinoma, a type of liver cancer, in adults. Vismodegib is an inhibitor of the Hedgehog pathway, which is thought to play a role in the development of hepatocellular carcinoma. Combined drug therapies can be used to increase the effectiveness of cancer treatment. Loading drugs used in cancer treatment into drug delivery systems is an accepted approach to reduce side effects and increase therapeutic efficacy. The aim of the study was to load these two hydrophobic drugs into the liposomal system, to examine their synergistic effects and to investigate their therapeutic efficacy on liver cancer in vitro. Liposomes prepared by thin lipid film hydration method were loaded with sorafenib and vismodegib drugs together. Optimization and characterization studies, in vitro drug release, stability and hemolysis experiments of the dual drug loaded liposome were performed. Also in vitro cytotoxicity and apoptotic effect of dual drug loaded liposomes were investigated. According to the obtained data, it was determined that the liposomal drug delivery system had appropriate characteristics, released the drugs in a controlled manner, did not cause hemolysis, and had cytotoxic and apoptotic effects on hepatocellular carcinoma cells. However, it was determined that the dual drug-loaded liposomal system did not cause toxicity in healthy human cells. As a result, it can be concluded that the obtained dual drug-loaded delivery system has the potential to be used in the treatment of liver cancer with reduced side effects and increased therapeutic efficacy. Keywords: liver cancer, sorafenib, vismodegib, liposomal drug delivery, dual therapy