Development of rapidly soluble mebendazole nanosuspension for colorectal cancer

Abstract

Mebendazole (MBZ) has been proven as a repurposing molecule against colorectal cancer. Unfortunately, its clinical application is constrained by its extremely poor solubility and bioavailability. The aim of the current work was to augment the dissolution rate at colonic pH and the anticancer efficacy by formulating MBZ nanosuspension (NS). A robust MBZ NS was developed using a combination of Sodium Lauryl Sulphate (SLS) and Hydroxy Propyl Methyl Cellulose E5 (HPMC) as stabilizers through the dual centrifugation method. The prepared MBZ NS exhibited the smallest particle size (362.6 ± 12.3 nm) with unimodal particle size distribution and excellent short-term stability. DSC and FT-IR studies confirmed the crystallinity and the absence of interactions with the stabilizers used. The developed MBZ NS demonstrated ∼20 folds higher dissolution than MBZ alone in colonic pH. Cell experiments showed that HPMC E5 and SLS were safe on HT-29 and HT-116 cell lines. In addition, IC50 of MBZ-NS was found to be 1.028 ± 0.030 μM and 0.884 ± 0.050 μM in HT-29 and HT-116 cell lines, respectively. Furthermore, 1.5 folds and 1.8 folds reduction in 3D tumor spheroids after treatment with MBZ-NS was observed compared to the control and MBZ physical mixture. From the In Vitro Live/Dead Cell Assay higher amount of red fluorescence in treatment groups confirmed a large number of dead cells compared to the control. In a nutshell, the produced MBZ NS could be employed as a promising formulation to achieve a higher dissolution rate and anticancer efficacy against colorectal cancer of repurposing drug MBZ.