Dose-Dependent Efficacy of Umbelliferone and Gelatin-Coated ZnO/ZnS Core-Shell Nanoparticles: A Novel Arthritis Agent for Severe Knee Arthritis

Abstract

Rheumatoid arthritis (RA) is a well-known autoimmune disorder that affects 1% of the global population. Zinc (Zn) is crucial for bone homeostasis, when compared with normal human bone, Zn level found to be decreased in RA patients and collagen-induced arthritis (CIA) rats. Notably, Zn-based medicinal products play a prominent role in reducing disease symptoms and acute side effects of patients with bone-related diseases. In this study, we report the clinical efficiency of gelatin- (Gel-) coated ZnO-ZnS core-shell nanoparticles (CSNPs) with umbelliferon (Uf) drug (Uf-Gel-ZnO-ZnS CSNPs) on the normal and CIA-induced Wistar rats. The formed ZnO-ZnS CSNPs are spherical in shape, with an average particle diameter of $150\pm 7\text{nm}$ . It showed strong cytocompatibility when tested on L929 and foreskin fibroblasts (BJ) cells by MTT assay. While comparing with free Uf, various doses (2.5 and 5 mg) of Uf-Gel-ZnO-ZnS CSNPs showed strong inhibition of CIA by attenuated proinflammatory cytokines such as interleukin-1β, IL-6, PEG2, and IL-17. The Uf-Gel-ZnO-ZnS CSNPs show more effectiveness in reducing joint swelling and also increase the level of antioxidant enzymes. In addition, CSNPs significantly reduced the infiltration of inflammatory cells in the knee joint. Thus, the current study concludes that Uf-Gel-ZnO-ZnS CSNPs feasibly reduce the incidence of arthritis in a dose-dependent manner by attenuation of inflammation.