In vivo evaluation of mebendazole and Ran GTPase inhibition in breast cancer model system.

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo. Graphical abstract Summary points In this study, we developed and characterized nanostructured lipid carriers (NLCs) loaded with mebendazole (MBZ; NLC-MBZ). NLC-MBZ was prepared to investigate its in vitro and in vivo anticancer effects. NLC-MBZ was explored for its inhibitory impact on RanGTP and its potential as an antimetastatic agent in mouse models. NLC-MBZ displayed a size of 155 ± 20 nm with a -27 ± 0.5-mV charge and 90.7% encapsulation efficiency. After 48 h of exposure, the IC₅₀ for free MBZ and NLC-MBZ was 610 and 305 nM, respectively, against MDA-MB-231 breast cancer cell lines. Moreover, NLC-MBZ reduced the size of the primary tumor and inhibited the development of lung metastases. NLC-MBZ reduced the expression CDC25A, SKP2, RbX1 and Cullin1 while increasing the expression of Rb proteins. NLC-MBZ showed antiangiogenic potential that resulted in a reduced rate of lung metastasis in vivo. [ABSTRACT FROM AUTHOR]