When nanotechnology is used in medicine, it makes it easier to find and treat a wide range of diseases. The potentially fatal disease multiple sclerosis (MS) has a disproportionately large impact on young people. One of the oral options for treating this condition is dimethyl fumarate (DMF). This study aimed to use platelet membranes and polymeric nanoparticles (PNs) to develop a drug delivery system that mimics biological cells to treat MS. Here, we produced and characterized solid lipid nanoparticles (SLNs) containing dimethyl fumarate (DMF). To make SLNs, DMF is combined with biocompatible lipids using hot emulsion and ultrasonication techniques. These DMF-SLNs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), FTIR spectroscopy, and a zeta meter instrument. Characterization revealed that the optimal SLNs had a polydispersity index of (0.28, 0.96, 0.77), a zeta potential of (-22.73 mV, -28.7 mV, and -30.13 mV), and a mean particle size of (562 nm, 1997 nm, and 849 nm). The results of this study suggest that the present formulation may be a potential longer-acting formulation for the improved management of MS. SLNs could significantly change the treatment of many illnesses by providing effective drug delivery.

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).
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).
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 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.

Glioblastoma multiforme (GBM), the most frequent malignant and aggressive primary brain tumor, is characterized by genetically unstable heterogeneous cells, diffused growth pattern, microvascular proliferation, and resistance to chemotherapy. Extensive investigations are being carried out to identify the molecular origin of resistance to chemo- and radio-therapy in GBM and find novel targets for therapy to improve overall survival rate. Dimethyl fumarate (DMF) has been shown to be a safe drug with limited short and long-term side effects, and fumaric acid esters (FAEs), including DMF, present both anti-oxidative and anti-inflammatory activity in different cell types and tissues. DMF has also anti-tumoral and neuroprotective effects and so it could be repurposed in the treatment of this invasive tumor in the future. Here, we have reviewed DMF pharmacokinetics and different mechanisms by which DMF could have therapeutic effects on GBM.

Methotrexate (MTX), a folate antagonist used to treat cancer and inflammatory diseases, isknownto generate reactive oxygen species.

The research investigates the impact of dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on an MTX-induced mouse hepatotoxicity model.

Forty-two mice were divided into 6 groups: control, MTX, DMF 120, and 3 groups of MTX co-treated with DMF 30, 60, and 120 mg/kg. Dimethyl fumarate was gavaged once daily for 10 days. On the fifth day, the animals received MTX 20 mg/kg intraperitoneally. On the eleventh day, the animals were sacrificed, and serum and liver samples were collected to assess the level of oxidative/anti-oxidative and apoptotic/anti-apoptotic markers.

Dimethyl fumarate prevented the increase of liver function enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) induced by MTX (P < 0.001). It prevented the increase in AST and ALT levels, indicating liver recovery (P < 0.001). Furthermore, DMF restored antioxidant markers superoxide dismutase, catalase, glutathione peroxidase, and total thiol while reducing the level of thiobarbituric acid reactive substances (P < 0.001). Dimethyl fumarate also downregulated hepatic mRNA expression of caspase 3 and upregulated Bcl-2, heme oxygenase 1, and Nrf2 genes in MTX co-treated DMF groups.

Dimethyl fumarate alleviates oxidative stress and apoptosis, which may be achieved by the Nrf2/HO-1 pathway. Therefore, DMF may be clinically effective in preventing or treating MTX-induced hepatotoxicity.

Three oral drugs, including fingolimod, dimethyl fumarate, and teriflunomide, which are clinically approved for the therapy of relapsing–remitting multiple sclerosis (RRMS) were reviewed in this work. The present study aimed to recognize the side effects of the oral drugs in RRMS patients who were consulted in neurology clinic in west of Iran.

The study population of the present prospective observational study conducted in 2016-2017 were patients with relapsing-remitting MS referred to Imam Khomeini Hospital (RA). Three hundred patients with RRMS were randomly assigned to three treatment groups. The first group received fingolimod, the second group received dimethyl fumarate, and the third group received teriflunomide. The response to treatment assessed at 1, 3, 6, 12, and 24 months after the start of treatment. Eventually, the frequency of adverse effects characterized for each group and the collected data compared in each treatment group. The collected data were analyzed using ANOVA statistical tests.

The findings of the present study revealed that the most common clinical complications were neurological (21.8%) and gastrointestinal complications (15.6%). The most common laboratory complications were liver (12.9%) and cardiovascular complications (10.3%). Moreover, the lowest clinical complications were musculoskeletal (4.6%) and endocrine complications (3%) and lowest laboratory complications were macular edema (0.6%).

In the present study, fingolimod had the most side effects and triflunomide had the least side effects. Dimethyl fumarate was stopped due to the severity of side effects and triflunomide was continued.

Cerebral ischemia is an important cause of morbidity and mortality worldwide. Dimethyl fumarate (DMF) is indicated for the treatment of patients with relapsing forms of Multiple Sclerosis and psoriasis.

In this study, the effect of DMF on memory and learning impairments and nitrosative stress after cerebral ischemia in rats, was evaluated.

Cerebral ischemia was induced via common carotid artery occlusion (CCAO). Rats were randomly divided into three groups (N = 5). Group I included Sham-operated animals who underwent surgery without arterial occlusions, group II (control ischemic) underwent surgery to induce transient global cerebral ischemia for 20 min and received 0.2 - 0.25 mL of distilled water, twice a day by oral gavage, group III included rats which underwent cerebral ischemia and then received DMF (15 mg/kg, twice daily, for 1 week) by oral gavage. Morris water maze test was used to assess spatial memory. Nitric oxide (NO) level in the hippocampus was measured using Griess test.

Treatment of rats with DMF (15 mg/kg, orally, twice daily for 7 days) resulted in a significant decrease in escape latency during training trials. Besides, the time spent in the target quadrant and the number of crossings over the platform area were significantly increased in the DMF-treated rats which were accompanied by a decrease in the proximity to the platform in the probe trial. Furthermore, the results of the Griess assay indicated a significant reduction in the NO levels in the hippocampus of DMF-treated rats.

Overall, our findings indicate that DMF improves memory impairment induced by cerebral ischemia/reperfusion injury in rats through the suppression of nitrosative stress in the hippocampus.

Currently available disease modifying anti-rheumatoid drugs have limitations like dose-dependent toxicity and tolerance.Dimethyl fumarate has demonstrated anti-inflammatory and immunomodulatory properties in various animal models. Thus, thepresent study aimed to evaluate the effects and mechanism of DMF in a murine model of adjuvant-induced arthritis.A total of 84 rats were divided into early treatment groups (n=48) and late treatment groups (n=36). There were 8 subgroupsand 6 subgroups (n=6 in each group) in the early and late treatment groups, respectively. Experimental rheumatoid arthritis(RA) was induced in Wistar rats by injecting complete Freund's adjuvant (CFA) intradermally at the base of the tail. Antirheumatic effects were evaluated by arthritis and histopathological scoring of ankle joints. To evaluate anti-oxidant properties,GSH, catalase, SOD, and lipid peroxidation were measured. ESR, WBC count, TNF-α and IL-6 levels were measured to evaluatethe immunomodulatory properties of DMF. DMF demonstrated anti-inflammatory effects by decreasing arthritis andhistopathological scores compared to the CFA control group, though the difference was not statistically significant. DMFexhibited immunomodulatory properties as decreases in TLC count, serum TNF-α, and plasma IL-6 levels were observed. In allthe above-mentioned parameters, the best response was achieved with the early combination therapy of DMF 30 mg/kg andmethotrexate [Mtx] 0.1 mg/kg. In the present study, DMF demonstrated antirheumatoid effects in a rat model of CFA-inducedarthritis. The best antirheumatoid effect was achieved with the early combination of DMF and Mtx.

Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS.

The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question.

A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment.

The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.

Dosimetry is a fundamental part of the radiation processing industry. Aqueous inorganic dosimeters have been used for gamma radiation dosimetry such as standard ferrous sulfate dosimeter. The purpose of this study was to investigate the effect of gamma radiation on the diethyl fumarate DEF in dimethyl sulfoxide DMSO solution and its possible use in chemical dosimetry. Three solutions having different concentrations of DEF were prepared (5, 10 and 20%) and exposed to various gamma doses. Irradiation was carried out using ROBO facility of 60Co gamma ray. Absorbance was measured using Melton Roy 1201 UV-VIS spectrophotometer. The absorption spectra of irradiated solution showed broad absorption bands between (325-400nm) with a shoulder at 332 nm. The absorbance increased with increasing the dose. Good response and linear relationship were found between absorbed dose and absorbance of 10% and 20% DEF concentration in the range of 0-225 kGy at the measured wavelength. Good dose rate independence was observed in the range of 14-33 kGy/h. It was noticed that irradiated samples had a good stability in darkness. Whereas, the response was affected during the storage in day light. This response was found to be depended on the irradiation temperature within the range of 18- 52 0C. Our measurements showed that the ability of using the solution of diethyl fumarate DEF in dimethyl sulfoxide DMSO as a high dose radiation dosimetry. The useful dose range for 10% and 20% DEF of concentrations is up to 225 kGy. Nevertheless, the correction of temperature for routine dosimetry measurements should be taken into account.

This work is related to optimize the porous structure nanocomposites based on polypropylene fumarate/ hydroxyethyl methacrylate/ bioactive glass nanoparticles (PPF/HEMA/NBG) which are cross-linked through the Reduction-Oxidation reaction (free radical polymerization) at the room temperature. The porous structures prepared by immersion of the nanocomposites in simulated body fluid (SBF) for 4 weeks. The samples were optimized based on the PPF/HEMA ratio, the NBG content and percentage of the benzoyl peroxide and dimethyl aniline pairs (BPOೀ) with mechanical strength (compressive strength) and surface morphology (SEM images) analyses. Finally, the best structure based on mentioned factors, SPHB.732/1.5, which contains the PPF/HEMA ratio at 30/70, NBG content at 20 wt% and BPOೀ pairs at 1.5 wt% was introduced as the optimum structure. This structure has an elastic modulus of 57.7 Mpa, interconnected-open porous architecture with the pore size approximately 100-200?m and the surface coated with hydroxycarbonate apatite microparticles (HCA). The SPHB.732/1.5 structure prepared by soaking in SBF not only is a bioactive component but also is a biodegradable material and hence can be used as a bone scaffold when more evaluate for this application.