Objective: Dimethyl fumarate (DMF) is a methyl ester of fumaric acid. It has been approved by USFDA recently for the treatment of an autoimmune disorder, multiple sclerosis (MS). The objective of present study was to synthesize and optimize chitosan loaded nanoparticles of DMF by box-behnken design (BBD), to provide a better drug delivery system for the management and treatment of MS.
Methods: Polyelectrolyte complex coacervation technique was used to prepare Chitosan (CS) loaded DMF nanoparticles and box behnken design using 3 factors and 3 levels were selected for optimization of the formulation. Effect of three independent factors that is, polymer CS concentration, polymer dextran sulfate (DS) concentration and the amount of drug were studied on two dependent responses that is particle size and % drug entrapment efficiency. The analysis of variance (ANOVA) was performed to evaluate the significant differences between the independent variables.
Results: The optimized batch showed the highest % drug entrapment (65.36) and an average particle size (355 nm). Zeta potential value was optimum to maintain the stability of the formulation. In vitro drug release behavior followed Korsmeyer-Peppas model which showed the initial release of 21.7±1.3% with prolonged drug release of 69.5±0.8% from optimized CS nanoparticle up to 24 h. The % cumulative drug release (% CDR) of optimized nanoparticles was 84%.
Conclusion: The optimized nanoparticles of DMF with improved properties could be a promising formulation for the treatment and management of MS
