Innovative rheumatoid arthritis management using injection replacement approach via dual therapeutic effects of hyalurosomes-encapsulated luteolin and dexamethasone.

Rheumatoid arthritis is a highly prevalent debilitating condition linked to inflammation. The effectiveness of the present therapeutic techniques is constrained; so, there is an urgent requirement for a novel nanoplatform entailing drugs with proven efficacy. The current work highlighted the development of dexamethasone and luteolin co-encapsulated hyalurosomes (LUT-DEX hyalurosomes). High entrapment efficiency of 92.79 % and 81.21 % for DEX and LUT, respectively in addition to sustained release of both drugs were attained, where only 45 % DEX and 75.87 % LUT were released after 24 h indicating the possibility of a persistent therapeutic impact. A spherical nano-system with smooth edges and a characteristic layer of hyaluronic acid surrounding the core of the particles was evidenced by a transmission electron microscope. The efficacy of LUT-DEX hyalurosomes was evaluated in-vision vivo using a rat model of rheumatoid arthritis initiated by Complete Freund's Adjuvant (CFA). Histological examination and serum concentrations of malondialdehyde (MDA), interleukin 1ß (IL1ß), tumour necrosis factor-alpha (TNF-α), interleukin 3 (MMP-3), and nuclear factor (erythroid-derived) Like 2 NRF2) were also evaluated. The dual drug-loaded hyalurosomes demonstrated 2.9-, 3.2-, 2.5- and 2.7-fold decreases in MMP3, TNF-α, MDA and IL1, respectively, compared with the positive control group. Conversely, the negative control group demonstrated the highest NRF2 level followed by LUT-DEX hyalurosomes, comparison compared to the positive control group which demonstrated the lowest NRF2 level. The histological examination of the joints confirmed the superior effect of the dual drug encapsulated nano delivery system in reducing joint swelling and inflammation achieving similar results as the negative control group. Ultimately, the developed hyalurosomes co-encapsulating dexamethasone and luteolin, possess the potential to serve as a highly auspicious innovative strategy for managing rheumatoid arthritis.