In vitro and In vivo neuroprotective study of solid lipid nanoparticles loaded with dimethyl fumarate

توضیحات

ABSTRACT

Dimethyl fumarate (DMF) is a FDA approved oral medication used to treat patients with multiple sclerosis (MS). Biological half-life of DMF is about 1 h, and it is rapidly hydrolyzed to its active metabolite monomethyl fumarate. The objective of present study is to formulate and characterize DMF loaded solid lipid nanoparticles (SLNs) to overcome these limitations. Material and Methods: DMF loaded SLNs were prepared by hot microemulsion and sonication method. Stearic acid was used as lipid and soy lecithin was colipid. Results and Discussion: The synthesized SLNs offered an average particle size of 300 nm, polydispersity index <0.3, and zeta potential value of -34.89 mv. In vitro evaluation on human neuroblastoma SH-SY5Y cells confirmed to have a neuroprotective effect of these colloidal systems under oxidative stress. DMF loaded SLNs showed to increase cell viability under H2O2 induced cell apoptosis. Cuprizone mouse model for MS was used to evaluate the effect of DMF loaded SLNs on locomotion score. Conclusion: In vitro study also confirmed a better locomotion and motor coordination scores in .cuprizone mouse model for MS

INTRODUCTION

The neurodegenerative process with damage to axons and oligodendrocytes is thought to be the cause of permanent neurological impairment and disability; this is a key feature of the disease multiple sclerosis (MS). At
present, most available MS therapies are thought to exert their effects through immunomodulatory or  immunosuppressive functions .Although these treatments are effective at inhibiting immune cell-driven inflammation and reducing the relapse rate, they are ineffective at controlling the predominantly eurodegenerative processes that occur later in the disease course. Fumaric acid esters have been used since 1959 as a treatment for psoriasis. Dimethyl fumarate (DMF) is currently approved by FDA as a first-line treatment for lowering relapse rates in MS. DMF and monomethyl fumarate were able to activate the transcription factor nuclear factor-erythroid 2-related factor 2 pathways and subsequently induce the expression of antioxidant proteins. Oxidative stress is one of the major factors in the pathogenesis of MS and is readily apparent within experimental autoimmune   encephalomyelitis, a mouse model of MS, and also in MS lesions.

Year: ۲۰۱۸

Publisher : ELSEVIER

 By : Olaf Perdijk, Marloes van Splunter, Huub F. J. Savelkoul, Sylvia Brugman and R. J. Joost van Neerve

File Information: English Language/ 6 Page / size: 662 KB

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سال : ۱۳۹۶

ناشر : ELSEVIER

کاری از : اولاف پریدن، مارلو ون اسپانتر، هوب اف. جی ساوالکول، سیلویا بروگمن و ر. جی. ون نویر

اطلاعات فایل : زبان انگلیسی / 6 صفحه / حجم : KB 662

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