Rational formulation of saponin and dexamethasone for the synergistic treatment of rheumatoid arthritis in vivo

Rheumatoid arthritis (RA) is a common autoimmune disease, and the abnormal proliferation of fibroblast-like synoviocytes (FLSs) in inflamed joints plays a key role in the pathogenesis of RA, which has become an important therapeutic target for RA treatment. This work reported a facilely formulated nanoparticle from saponin (Sap) and dexamethasone (Dex) in precise ratio, affording the resultant Dex@Sap nanoparticles. Benefiting from the enlargement of vascular endothelial cell gap at the inflammation site and intra-articular injection, Dex@Sap could accumulate at the inflamed joints to inhibit excessive proliferation of FLSs and mediate cell apoptosis, achieving symptomatic relief and efficient RA treatment, while reducing the amount of drug needed as well as the occurrence of adverse reactions. Typical AKT (also known as protein kinase B, PKB)/mTOR (mammalian target of rapamycin) pathway was observed to be inhibited, and the mitochondria-mediated intracellular reactive oxygen species (ROS) level was also upregulated by Dex@Sap. Further evaluations demonstrated that Dex@Sap could significantly alleviate RA-induced inflammatory response and the expression of pro-inflammatory cytokines to cure joint damage in collagen-induced arthritis mice and rats. This work provides a clinically promising nanomedicine to synergistically treat RA.