Nanotransethosomal dual-drug loaded gel of methotrexate and mangiferin as a potent synergistic intervention for rheumatoid arthritis via transdermal delivery.

The goal of this study is to assess the potential advantages of utilising methotrexate (MTH), and mangiferin (MFR), in nanoparticulate configuration which could result in increased stability and solubility, as well as improved infiltration into the arthritic tissues under investigation. The synthesised MTH-MFR-TRS demonstrated a particle size of 151.7 nm and a PDI of 0.1199. Additionally, the zeta potential was observed to be favourable at -30.43 mV. Supplementary evaluations were performed, comprising transmission electron microscopy (TEM), confocal microscopy and skin permeation analysis. The CLSM study revealed that the MTH-MFR-TRS gel formulation demonstrated enhanced permeation of MTH and MFR through the skin layers in comparison with MTH-MFR suspension gel. The MTT assay conducted on Raw 264.7 and SW982 cell lines demonstrated a significant decrease (P < 0.05) in the IC50 value of the MTH-MFR-TRS formulation (9.0 mM and 60.8 mM, respectively) when compared to the drug suspension. The results of the in vivo investigation indicate that the MTH-MFR-TRS gel displays favourable anti-arthritic characteristics compared to the diclofenac standard gel. The aforementioned phenomenon was evidenced by means of histopathological investigations and radiographic scrutiny. The study at hand has validated the utility of TRS vesicles as a carrier for the transdermal administration of MTH and MFR, thereby offering a promising therapeutic approach for the management of rheumatoid arthritis.