Osteopontin-loaded PLGA nanoparticles enhance the intestinal mucosal barrier and alleviate inflammation via the NF-κB signaling pathway

Abstract

Osteopontin is a multifunctional glycoprotein that is secreted by a variety of tissues or cells, but the role of osteopontin in the epithelial mucosal barrier has not been clearly established. We loaded osteopontin into hyaluronic acid-functionalized polymeric nanoparticles, which were administered by gavage to a colitis mouse model. The disease activity index, weight gain and colon length were calculated to assess the degree of symptoms. Epithelial permeability was measured using fluorescein isothiocyanate-conjugated dextran. The enzymatic activity of myeloperoxidase in the colon and inflammatory cytokines were assayed to assess the levels of inflammation. The histological appearance of the colon was observed by H&E staining. Tight junction proteins and signaling pathway proteins (NF-κB and phospho-NF-κB) were determined by western blotting. The resultant spherical osteopontin-loaded nanoparticles were characterized by the expected particle size (approximately 272.3 nm) and a slightly negative zeta potential (approximately -5.3 mV). Interestingly, we found that the osteopontin-loaded nanoparticles exerted remedial effects on colitis by both enhancing the intestinal barrier and alleviating inflammation in vivo according to the tested parameters. These results suggest that OPN plays a positive role in protecting the epithelial mucosal barrier and may be a therapeutic drug in gut homeostasis.