Studies on the development of liposomal formulations for the use of NRF2 inhibitors in cancer treatment

Cancer is one of the leading causes of death in the world. There are numerous products on the market for the treatment of cancer, there are still formulations that are the subject of active clinical research. The use of Nrf2 inhibitors in the treatment of cancer is one of the innovative approaches. However potent and specific Nrf2 inhibitors with properties suitable for clinical application has not been formulated yet. The primary causes of this include toxicity, limited biological activity, and poor pharmacokinetic qualities, which result in an insufficient effect. The role of drug delivery systems in increasing the effectiveness of chemotherapeutic agents is known. Thermosensitive liposomes are promising in this field. Liposomes offer advantages such as targeting tumor cells, increasing cellular uptake and local drug release. In this thesis study, it was aimed to prepare thermosensitive liposome formulations of brusatol, an Nrf2 inhibitor, targeted to tumor, which can show high efficacy and low side-effect profile, and release active substance in tumoral tissue in order to increase the effectiveness in cancer treatment. In the study, after the formulation optimization with the QbD approach and artificial neural networks (ANN), characterization studies of the optimum formula were performed and its cytotoxic properties were investigated. Successful results were obtained as a result of in vitro characterization and cell culture studies with brusatol-loaded liposomes. It is thought that the prepared formula may allow the treatment of cancer and/or provide a synergistic effect in combination chemotherapy.