Neuroprotective Potential of Dimethyl Fumarate-loaded Polymeric Nanoparticles against Multiple Sclerosis

Abstract

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 effi ciency was found to be 65.36 % and the drug loading was 28 %. The formulation's in vitro drug release profi le 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 confi rmed these fi ndings by showing a signifi cant increase in locomotion score.

Nanotechnology‐empowered therapeutics targeting neurodegenerative diseases

“…Presently, no effective drugs were approved for the therapy of the disease and few therapeutics are utilized to mitigate the symptoms of only the early stages of the disease with low evidence levels. Recently, dimethyl fumarate loaded solid lipid nanoparticles (Ojha & Kumar, 2018) and chitosan nanoparticles (Ojha et al, 2019) were reported to significantly increase the bioavailability and neuroprotective effects in rat models. This data presented that nanotechnology was a potential strategy with an enhanced circulation for the better treatment of multiple sclerosis.…”

The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders

“…The main features of the disease reported to occur in early patients include cortical demyelination and meningeal inflammation ( Bø et al, 2003 ; Lucchinetti et al, 2011 ). Recent studies demonstrate that SL NPs and CS NPs can potentially increase the bioavailability and neuroprotective effects of a relapsing-MS drug dimethyl fumarate in rat model ( Ojha and Kumar, 2018 ; Ojha et al, 2019 ). Another study also suggests that glucocorticoids and inorganic–organic hybrid NPs can also be used to treat MS ( Montes-Cobos et al, 2017 ).…”

Recent Advances in Nanomedicines for Multiple Sclerosis Therapy

“…In an ethidium bromide-induced demyelination animal model study, Youssef et al 269 applied LINGO-1-directed siRNA-loaded chitosan nanoparticles and discovered that these nanomedicines could regulate the repair signal in histopathological sections, increase the expression of the pontine myelin basic protein, and reduce the activity of caspase-3 thus to induce the remyelination process and promote neuroprotection. Ojha et al 270 assessed the potential neuroprotective effect of dimethyl fumarate (DMF)-loaded chitosan (CS) dextran sulfate (DS) polymeric nanoparticles as therapeutic agents for a cuprizone model of MS. A significant increase in the locomotion score for the MS animal model indicated that the neuroprotective and therapeutic effect for MS was achieved by management of DMF-loaded CS-DS nanoparticles. These neuroprotective effects have also been confirmed by Elnaggar et al, 263 Hashemian et al, 261 Rong et al, 271 and Xu et al 272 in their studies on a variety of neurological disorders.…”