Sulfonated Bovine Serum Albumin Hydrogel for Anti-inflammatory Treatment of Rheumatoid Arthritis via Restoring Macrophage Phenotype

Rheumatoid arthritis (RA) is an autoimmune disease with high rates of late-stage disability. Unfortunately, effective treatments for RA are limited by side-effects and high cost of clinical drugs. Bovine serum albumin (BSA) with high biocompatibility and low cost is widely used as the carrier for drug delivery. Here, sulfonated BSA (sBSA) was first time synthesized and its hydrogel system with HA matrix (sBSA/HA) was prepared for RA treatment. In RAW 264.7 cells, sBSA, but not bare BSA, significantly reduced the generation of reactive oxygen species and pro-inflammatory cytokines induced by LPS to the normal levels or even below. The scavenger receptor on macrophages was identified responsible for the enhanced uptake of sulfonated BSA. In vivo, 3% sBSA/HA showed the abilities of anti-inflammation, bone protection and restoring clinical scores and claw thickness of healthy rats in collagen-induced arthritis (CIA). Compared with the positive control (methotrexate), sBSA/HA had significant advantages in terms of speed of action, treatment effectiveness, and duration. Notably, both sBSA and sBSA/HA promoted M2 polarization (P<0.001) by reducing the M1(CD86)/M2(CD206) phenotype ratio, suggesting the possible immune-modulation mechanism of sBSA in treating RA. Conclusively, sBSA was verified as a promising candidate for RA treatment.