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Background: Successful drug extraction from biological fluids is challenging due to interfering factors and the trace levels of the target analytes. background: Today, successful drug extraction, especially in biological fluids, due to interfering factors and the trace level of targeted analytics, faces many challenges in a complex matrix. Therefore, providing a suitable and sensitive method that can be increased the efficacy of extraction method has been considered. Objective: We aimed to provide a suitable and sensitive method to increase the efficiency of methotrexate extraction from biological fluids. objective: In this study, the chitosan-based nanogels, which were synthesized by the ionic gelation method were used for solid-phase microextraction of methotrexate Methods: Chitosan-based nanogel synthesized by the ionic gelation method was used for solidphase microextraction of methotrexate from aqueous and plasma media. The nanogel was characterized in vitro in terms of morphological characteristics (transmission electron microscopy), particle size, polydispersity index (PDI), and zeta potential. High-performance liquid chromatography was used to determine the methotrexate concentrations and extraction yield. method: The in vitro characterization of nanogels were performed by evaluation of morphological characteristics with TEM, determination of particle size, PDI, and zeta potential and also the HPLC assay method for determination of methotrexate concentration in different media and determination of extraction yield Results: A nanogel with an average size of 135.6 nm and PDI of 0.14 was used for the nanoextraction of methotrexate in this study. The methotrexate concentration, nanogel amount, and extraction time affected the extraction yield. Maximum recovery percentages of 75% and 69% were achieved when extracting methotrexate from aqueous and plasma media, respectively. result: The nanogels with the average size of 135.6 nm and PDI of 0.14 were used for nanoextraction of methotrexate in this study. The concentration of methotrexate, amount of nanogel, and time of extraction were evaluated as an essential factor affecting the extraction yield. Conclusion: The high extraction yields in both studied media indicate that using chitosan-based nanogel as a sorbent during the solid-phase microextraction of methotrexate is a promising prospect, with potential uses for other drugs in different media. It seems that using nanogels can be an excellent way to improve the extraction of drugs from biological environments. other: non

Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that involves young individuals. The drug delivery systems now are available for this disease have chronic and non-targeted effects in the patients, and because of the presence of BBB, their concentration in the CNS is low. Because of this flaw, it is critical to use innovative active targeted drug delivery methods. Platelets are blood cells that circulate freely and play an important role in blood hemostasis. In this review, we emphasize the various roles of activated platelets in the inflammatory condition to recruit other cells to the injured area and limit the inflammation. Besides, the activated platelets in the different stages of the MS disease play a significant role for limiting the progression of inflammation in the peripheral area and CNS. This evidence indicates that platelet-based drug delivery system can be an efficient candidate for drug targeting to the CNS and limiting the inflammation in the peripheral and central areas for MS therapy.

Dimethyl fumarate (DMF), is one of the lately approved therapeutic agents for the multiple sclerosis (MS) treatment. Despite the beneficial effects, DMF also suffers from low penetration into brain. In this study, we designed a precise drug delivery system of DMF to cross BBB for MS management. The novelty of this study is developing a cell based biomimetic vehicle for specific drug delivery to the inflamed area in peripheral and CNS. DMF-loaded platelet-based nanoparticle as a cell-based drug delivery system was developed and compared with chitosan nanogel and platelet membrane coated chitosan nanogel. Prepared nanoparticles were characterized for particle size, morphology, release characteristics, and drug loading parameters. In the optimum condition, all nanoparticles were prepared in desirable nano-size and showed appropriate loading parameters. The neuropharmacokinetic evaluation was performed by determining the brain uptake of DMF, and brain uptake clearance for passage from BBB. Results from in vivo study demonstrated that the brain concentration of nanoparticles was higher than the free drug solution. The brain uptake clearance and AUC (0-∞) brain of DMF-loaded platelet nanoparticle were higher than platelet membrane coated chitosan nanogel and chitosan nanogel. The results demonstrated that platelet nanoparticles can be proposed as a potential biomimetic carrier for MS management.

Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.