Development and fabrication of a novel nano-bilosomal system for enhanced oral delivery of Trametinib: apoptotic induction and anticancer efficacy evaluation

In order to inhibit growth factor-mediated cell signalling and cell proliferation in various cancers, Trametinib (TM) binds preferentially to Mitogen-Activated Protein Kinase Kinase 1 and 2 (MEK). This study marks a first impression in assessing the impact of bilosomes (BS) of TM on oral bioavailability. A thin-film hydration technique, and the optimisation was done using Box-Behnken Design. Quantities of sodium taurocholate (STC), cremophor EL and Span 60 were taken as independent variables. The optimized formulation depicted a low hydrodynamic diameter (158.32±10.24nm) and high entrapment efficiency (94.27±2.16%), zetapotential (-46.57±1.06 mV) and PDI (0.132±0.03). The TM-BS showed a biphasic release pattern and obtained significantly high penetration compared to the pure TM solution (p<.05). The modified formulation, which is an optimised TM-BS, demonstrated lower IC50 in comparison to A549 cells, according to the cytotoxic evaluation. Additionally, enhanced TM-BS dramatically raised cellular caspase-3 protein expression. The TM-BS killed A549 cells better than TM solution.