Niclosamide nanoemulsion for colorectal cancer: development, physicochemical characterization, and in vitro anticancer activity

The BCS class II (Biopharmaceutical Classification System) niclosamide has shown promising anticancer activity for colorectal cancer. However, its low water solubility compromises its oral absorption and systemic action. Incorporating niclosamide in nanoemulsion allows to optimize its cell uptake and tumor penetration. This study aimed at the development, physicochemical characterization, and in vitro anticancer activity of a niclosamide nanoemulsion, with HCT-116 as the cell model. Medium- and long-chain lipids were tested to prepare the nanoemulsions, obtained by high-pressure homogenization. Design of experiments was used to optimize the formulations, which were subjected to a stability study at 30 degrees C/75% relative humidity (RH) and 4 degrees C. Nanoemulsion efficacy was evaluated in an HCT-116 viability assay and 3D cell culture model. Medium-chain lipids provided better solubility results than long-chain. Miglyol (R) 812 and poloxamer 188 proved to be suitable components for the system. Niclosamide nanoemulsion (similar to 200 nm) was stable for 56 days, presenting monomodal particle size distribution. The cell viability assay with HCT-116 cell line demonstrated that niclosamide cytoxicity was both time and concentration dependent. In the 3D cell culture model, size and zeta potential may have influenced drug penetration in the spheroid. Incorporating the drug substance in a nanostructured system was pivotal to potentiate niclosamide activity. Our results encourage further research to understand and optimize niclosamide performance as an anticancer drug substance aiming at its repositioning.