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Abstract :
[en] Development of new chemotherapeutic agents remains a continuing challenge in oncology, as the disease represents the major cause of morbidity and mortality worldwide. Lung cancer is the most frequently diagnosed cancer and was the leading cause of deaths due to cancer in the last recent years [1]. In Belgium, one cancer out of four was associated to lung cancer in 2013 [2]. There is therefore an urgent need to discover new chemotherapeutic options. To date, the treatment of patients with lung cancer is a combination of surgery, radiotherapy and/or oral or IV chemotherapy. But there is currently no direct pulmonary treatment to administer chemotherapeutic drugs.
Our project seeks to develop an original formulation for inhalation based on liposomes and a natural compound from the flavonoid class to treat lung cancer. Previous work carried out in our laboratory showed that liposomes with a positive zeta potential and composed of DPPC, DOPE, DC-Cholesterol and DSPE-PEG2000 displayed superior entrapping rate of the active flavonoid. Starting from that formulation, we worked on the optimization with different types and proportions of lipids, and characterized the liposomes in terms of size, PDI, charge, encapsulation efficiency and drug loading capacity. The in vitro therapeutic efficacy and cytotoxicity of the formulations were validated by MTT assays on a lung cancer cell line (LLC - mouse Lewis lung carcinoma cells) and on a lung control cell line (MLE12). The formulation giving the optimal characteristics and response on cells will be then evaluated in vivo for its tumor potential and toxicity in a relevant experimental lung cancer mouse model.
