Amelioration of Freund's adjuvant-induced polyarthritis by Diosmin-loaded nanoparticles in Wistar rats; a mechanistic study.

Abstract

The current study aims to synthesize diosmin-loaded nanoparticles (DNPs) to make available an alternative safe treatment for adjuvant-induced polyarthritis. DNPs were formulated using chitosan biopolymer and characterized. Acute toxicity study was also performed and acute anti-inflammatory potential was accessed using phologistic agents. For anti-arthritic potential, disease was inoculated by injecting 0.15-ml Freund's adjuvant at day 1 to all groups except normal control in left hind paw. Therapy using DNPs at 5-20 mg/kg and diosmin 20 mg/kg and methotrexate was started from day 8-28 orally. The DNPs of size 223 nm, potential 2.9 Mv, polydisparity index > 0.7 and spherical shape particles as revealed by scanning electron microscopy and amorphous nature were revealed by X-ray diffraction. DNPs dose dependently ameliorated arthritic scoring, pain, paw swelling and body weight in contrary to disease control. DNPs and free drug restored significantly altered blood parameters, oxidation status and neurotransmitters level in treated animals as evident by histologic examination of tissues. Treatment with DNPs and free drug profoundly downregulated the expression of cyclooxygenase-2, interleukin (IL)-6, TNF-α, NF-κβ and increased IL-4 and IL-10 in arthritic animals. DNP 20 mg/kg revealed noteworthy anti-arthritic, anti-inflammatory and anti-nociceptive potential in counter to diosmin and methotrexate treated animals.