May-June 2019 Indian Journal of Pharmaceutical Sciences 496 Research Paper The neurodegenerative process is a key step in the pathogenesis of multiple sclerosis (MS) with symptoms of permanent neurological disability and impairment [1,2] . Currently, most available MS therapeutic agents are immunomodulatory or immunosuppressive in nature [3-5] and effectively inhibit immune cell-driven inflammation thus reduce the relapse rate. But they do not control the predominant neurodegenerative processes that mainly occur later in the disease course [6] . Dimethyl fumarate (DMF) is a fumaric acid ester that has been used since 1959 for the treatment of psoriasis [7] . FDA has now approved DMF as a first line oral treatment for lowering relapse rates in MS [8-11] . DMF and its active metabolite monomethyl fumarate (MMF) have antioxidant property by activation of the transcription factor, nuclear factor-erythroid derived 2-factor pathways [12-14] . Oxidative stress is one of the key factors for neuron degeneration and pathogenesis of MS disease, which is evidenced within MS lesions, and also in experimental autoimmune encephalomyelitis, a mouse model of MS [15] . In last decade, nanotechnology has proved its effectiveness for the diagnosis and treatment of variety of immune-mediated diseases. In the present study, chitosan (CS) dextran sulphate (DS) nanoparticles loaded with DMF were prepared using the polyelectrolyte complex coaservation technique and the nanoparticles’ zeta potential and average particle size were measured. CS is a biocompatible, biodegradable, low toxic, cationic polymer with mucoadhesive properties. Polymeric nanoparticulate drug delivery systems offer enhanced penetrating ability of molecules across mucosal surfaces, good systemic availability, targeted drug delivery, improved pharmacokinetic profile, better half-life and drug pay load. Now a days nanotechnology offers a promising results and effective platform for many industrial and medical fields [16,17] . The developed CS-DS nanoparticles were further evaluated in vitro in human neuroblastoma SH-SY5Y cells and in an established cuprizone animal model in vivo. Neuroprotective Potential of Dimethyl Fumarate-loaded Polymeric Nanoparticles against Multiple Sclerosis SMRITI OJHA*, BABITA KUMAR 1 AND HINA CHADHA Vishveshwarya Group of Institutions, Department of Pharmacy, G. B. Nagar, Noida-203 207, 1 Sanskar Educational Group, Department of Pharmacy, Ghaziabad-201 302, India Ojha et al.: Development of Dimethyl Fumarate-loaded Chitosan Nanoparticles The aim of the present study was to access the potential of dimethyl fumarate-loaded chitosan polymeric nanoparticles for the management of multiple sclerosis. Dimethyl fumarate-loaded chitosan nanoparticles were prepared by polyelectrolyte complex coaservation technique. The prepared nanoparticles were characterized and found to have an average particle size of 324 nm, zeta potential of –34.85 mV and a poly dispersity index of 0.367. The entrapment efficiency was found to be 65.36 % and the drug loading was 28 %. The formulation’s in vitro drug release profile and stability parameters were also evaluated. Cumulative percent drug release was found to be 84 % up to 24 hours and the formulation was found to be stable at 28° for 90 days. In vitro neuroprotective effect of the nanoformulation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human neuroblast SH-SY5Y cells and the treated cells showed improved cell viability under hydrogen peroxide-induced cell apoptosis. In vivo cuprizone model for multiple sclerosis in rodents also confirmed these findings by showing a significant increase in locomotion score. Key words: Multiple sclerosis, chitosan nanoparticles, cuprizone model, SH-SY5Y cells, bioavailability *Address for correspondence E-mail: smritiojha23@gmail.com This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms Accepted 12 April 2019 Revised 23 December 2018 Received 03 September 2018 Indian J Pharm Sci 2019;81(3):496-502