Preparation and Statistical Modeling of Solid Lipid Nanoparticles of Dimethyl Fumarate for Better Management of Multiple Sclerosis

Abstract

Purpose: The objective of this study was to synthesize and statistically optimize dimethyl fumarate (DMF) loaded solid lipid nanoparticles (SLNs) for better management of multiple sclerosis (MS). Methods: SLNs were formulated by hot emulsion, ultrasonication method and optimized with response surface methodology (RSM). A three factor and three level box-behnken design was used to demonstrate the role of polynomial quadratic equation and contour plots in predicting the effect of independent variables on dependent responses that were particle size and % entrapment efficiency (%EE). Results: The results were analyzed by analysis of variance (ANOVA) to evaluate the significant differences between the independent variables. The optimized SLNs were characterized and found to have an average particle size of 300 nm, zeta potential value of -34.89 mv and polydispersity index value < 0.3. Entrapment efficiency was found to be 59% and drug loading was 15%. TEM microphotograph revealed spherical shape and no aggregation of nanoparticles. In-vitro drug release profile was an indicative of prolonged therapy. In-vivo pharmacokinetic data revealed that the relative bioavailability was enhanced in DMF loaded SLNs in Wistar rats. Conclusion: This study showed that the present formulation with improved characteristics can be a promising formulation with a longer half-life for the better management of MS.

Keywords: Box-behnken design, Dimethyl Fumarate, Multiple Sclerosis, Response Surface Method, Solid lipid nanoparticles, Polydispersity index