Fabrication of hesperidin hybrid lecithin-folic acid silver nanoparticles and its evaluation as anti-arthritis formulation in autoimmune arthritic rat model

Abstract

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction and loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to adverse effects and patient non-compliance. Hesperidin (HP) is a naturally occurring bioflavonoid having anti-inflammatory and antioxidant properties. In this study, Hesperidin loaded hybrid lecithin-folic acid silver nanoparticles (L-HP-FA-AgNPs) formulation has been developed to deliver HP to inflamed jointsspecifically.Thein vivo anti-inflammatory and anti-arthritic effectsof the formulation were validated in the CFA arthritis rat model by giving oral treatment of L-HP-FA-AgNPs (1 and 3mg/kg) which alleviated the joint swelling, cartilage destruction and reduced influx of inflammatory cells. The results showed decreased pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in the peritoneal and spleen cells coupled with an increase in anti-inflammatory cytokine TGF-β1. Additionally, the treatment caused the decline in M1 macrophage activation with a concomitant increment in M2 macrophage activation. Further, hybrid L-HP-FA-AgNPs suppressed the production of RANKL, OPG and MMP-2/9, which supported its anti-osteoclastic effects. Collectively, our data revealed that L-HP-FA-AgNPs significantly inhibited the progression of arthritis by reducing inflammationand bone damage. The protective effects of hybrid L-HP-FA-AgNPs highlight its potential as an ideal new anti-arthritic agent for human RA.