Development of rapidly soluble mebendazole nanosuspension forcolorectal cancer

Abstract

Mebendazole (MBZ) has been proven as a repurposing molecule against colorectal cancer. Unfortunately, its clinical application isconstrained by its extremely poor solubility and bioavailability. The aim of the current work was to augment the dissolution rate atcolonic pH and the anticancer efficacy by formulating MBZ nanosuspension (NS). A robust MBZ NS was developed using a combination ofSodium Lauryl Sulphate (SLS) and Hydroxy Propyl Methyl Cellulose E5 (HPMC) as stabilizers through the dual centrifugation method. Theprepared MBZ NS exhibited the smallest particle size (362.6 ± 12.3 nm) with unimodal particle size distribution and excellent short-termstability. DSC and FT-IR studies confirmed the crystallinity and the absence of interactions with the stabilizers used. The developed MBZNS demonstrated ∼20 folds higher dissolution than MBZ alone in colonic pH. Cell experiments showed that HPMC E5 and SLS were safe onHT-29 and HT-116 cell lines. In addition, IC of MBZ-NS was found to be 1.028 ± 0.030 μM and 0.884 ± 0.050 μM in HT-29 and HT-116 celllines, respectively. Furthermore, 1.5 folds and 1.8 folds reduction in 3D tumor spheroids after treatment with MBZ-NS was observedcompared to the control and MBZ physical mixture. From the In Vitro Live/Dead Cell Assay higher amount of red fluorescence in treatmentgroups confirmed a large number of dead cells compared to the control. In a nutshell, the produced MBZ NS could be employed as apromising formulation to achieve a higher dissolution rate and anticancer efficacy against colorectal cancer of repurposing drug MBZ.