Diosgenin loaded-chitosan biodegradable nanoparticles ameliorate adjuvant-induced arthritis, pain, and peripheral neuropathy through moderation of inflammatory and oxidative stress biomarkers.

This research work was designed to develop efficient Diosgenin (DGN) loaded biodegradable nanoparticles (DGN-NPs) for treating rheumatoid arthritis. The DGN-NPs were synthesized by ionic-gelation method using chitosan as a biodegradable polymer and in-vitro release study was performed followed by kinetics study. DGN-NPs had an average size of 290 nm, zeta potential of +11.5 mV with 72 % entrapment efficiency, and PDI of 0.398. XRD analysis of DGN-NPs indicated the crystallographic nature while SEM analysis showed the spherical morphology and smooth surface. The release of DGN from NPs occurred by diffusion and erosion mechanism. The anti-arthritic potential of DGN-NPs was investigated by injecting 0.1 ml Complete Freund's adjuvant in the left hind paw of Wistar rats on day 1 while oral therapy with DGN 15 mg/kg, and DGN-NPs at 5, 10, and 15 mg/kg was carried daily. Methotrexate (1 mg/kg) served as standard and was started on day 8 and continued till the 28th day by oral route. The DGN-NPs notably (p < 0.05-0.0001) reduced paw edema, pain, arthritic scoring, and improved body weight in contrast to DGN and standard therapy. The oxidative stress biomarkers were restored by GDN-NPs in the liver and sciatic nerve homogenates along with restoration of altered blood parameters as compared to disease control. The level of serotonin and nor-adrenaline in sciatic nerve homogenates was also profoundly elevated in DGN-NPs-treated arthritic rats. Treatment with DGN-NPs significantly (p < 0.01-0.0001) downregulated NF-κβ, IL-6, IL-1β, COX-2, and TNF-α while upregulated IL-4 in contrast to disease control which resulted in the improvement of the histological lesions in ankle joints and sciatic nerve. It can be inferred from the current study that DGN-NPs especially at 15 mg/kg exhibited notable anti-arthritic, and analgesic activity in contrast to DGN. Moreover, DGN-NPs are also effective against peripheral neuropathy.