Fabrication of Mebendazole Loaded Solid Lipid Nanoparticles: Formulation, Optimization, Characterization, Stabilization, and In-Vitro Evaluation

Abstract

Mebendazole (MBZ), a general treatment benzimidazole based anthelmintic agent, has low aqueous solubility and oral bioavailability, which limits its therapeutic applications in treating systemic parasitic infections and cancer. Through application of the nanotechnology based drug delivery techniques, especially the solid lipid nanoparticle (SLNs) the drug delivery techniques can be subjected to improvement of the solubility, stability and the controlled release of the drugs. In this work, preparation, optimization, characterization, and in-vitro-study of Mebendazole-loaded solid lipid nanoparticles (MBZ-SLNs) were reported. The nanoparticles have been prepared by employing the formula of solvent emulsification-evaporation technique, using stearic acid as lipid matrix and poloxamer 188 as a surfactant. Variables in formulation like the ratio of lipid to drug, the concentration of the surfactants and the speed of homogenisation were optimised as per a central composite strategy. The characterization was done in terms of particle size, zeta potential, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Stabilization tests were carried out according to ICH guidelines and at different storage conditions and in-vitro release of drugs was assessed in simulation of gastric and intestinal fluids. Experiments yielded values of mean particle size of 180 +/- 12nm, zeta of -28.5mV, 92.4+/-1.6 entrapped percentage, and sustained release of 24hours with higher order correlation with Higuchi diffusion. Physicochemical stability results showed a high-quality physical integrity within three months Cytotoxicity was studied in-vitro on HeLa cells and the results showed increased antiproliferative activity compared to free MBZ suspension. The results show that MBZ-SLNs could be a prospective drug delivery system to improve the efficacy of Mebendazole against parasitic and oncological diseases.