Esculin-loaded nanoparticles ameliorate adjuvant-induced polyarthritis via subduing inflammatory and oxidative stress biomarkers in Wistar rats

Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed. ENPs were synthesized using the ion gelation method and their characterization was done. The formulated ENPs had a particle size of 205.1 nm, a polydispersity index of 0.574, zeta potential of 3.6 ± 0.1 mV, and entrapment efficiency of 68%, SEM analysis showed round spherical and irregularity from the outer surface, XRD revealed amorphous nature. Drug release from the carrier by erosion method. For anti-arthritic potential, 0.1 ml Complete Freund's Adjuvant was injected in the left hind paw of all Wistar rats except normal rats on day 1 and treatment with ENPS at 5, 10, 20, ESC and methotrexate (standard drug) was started at 8th day orally and continued for 21 days. Treatment with methotrexate, ESC, and ENPs revealed a significant reduction of paw edema and pain, restoration of body and immune organ weight, Treatment with ENPs 20 mg/kg remarkably (p < 0.0001) restored serotonin and noradrenaline level, oxidation status, hematological and biochemical parameters with significant down-regulation (p < 0.0001) of IL-6, COX-2, TNF-alpha, NF-κβ whereas, up-regulation of IL-4 and IL-10 in comparison to disease control group as obvious from histological examination of sciatic nerve, liver, and ankle joint. The LD₅₀ of ENPs was more than 2000 mg/kg in the acute toxicity study. The ENPs exhibited anti-inflammatory and anti-arthritic activities especially ENPs at 20 mg/kg.