In vitro evaluation of lipidic nanocarriers for mebendazole delivery to improve anticancer activity

Enhance the anticancer activity of the repurposed drug Mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs). MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment. NLCs were prepared by mixing different ratios of solid lipid (Stearic acid) and liquid lipid (Oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC₅₀ assays and in vitro scratch assays. The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of -27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC₅₀ of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell-cell contact, further supporting their potential for improved therapeutic efficacy. MBZ-NLCs exhibit significantly improved stability, encapsulation efficiency, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.