Development and evaluation of venetoclax and siRNA loaded albumin based carrier systems

Cancer, a worldwide health problem is the result of a tumor formation characterized by uncontrolled cell proliferation. Bcl-2 protein encoded by the Bcl-2 gene plays a significant role in controlling apoptosis and increasing cell survival in response to various apoptotic stimuli. Venetoclax (ABT199) is the first FDA approved drug to suppress the Bcl-2 gene and used in the treatment of patients with chronic lymphocytic leukemia (CLL). Also the studies on siRNAs that suppress the Bcl-2 gene have increased. In cancer cells overexpressing Bcl-2, growth is inhibited and the sensitivity of cancer cells to chemotherapy is increased by the Bcl-2 gene is specifically targeted by siRNA and down-regulated. The combined use of the anticancer drug and siRNA can synergistically increase therapeutic efficacy by selective targeting and reducing drug resistance. The purpose of this study was to determine the physicochemical properties of these formulas and to overexpress the Bcl-2 gene separately and together (siRNA/ABT) into the albümin nanoparticles, which were used in the clinic to suppress the Bcl-2 gene in vitro. As a result it is aimed to evaluate the efficacy of Venetoclax in breast cancer and to minimize the toxic effects by using a carrier system.