Injectable hyaluronic acid–tyramine hydrogels for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading in turn to articular cartilage destruction. In this work, injectable tyramine modified hyaluronic acid (HA–Tyr) hydrogels were developed for the treatment of RA. HA–Tyr conjugate was synthesized by amide bond formation between carboxyl groups of HA and amine groups of tyramine. Then, HA–Tyr hydrogels were prepared by radical crosslinking reaction using H2O2 and horse-radish peroxidase. Intra-articular injection of HA–Tyr hydrogels encapsulating dexamethasone (DMT) as a model drug resulted in successful treatment of RA with reduced interlukine-6, prostaglandin E2 and four types of cytokine levels in collagen-induced arthritis animal models. Histological analysis with hematoxylin and eosin (H&E) staining also confirmed the therapeutic effect of injectable HA–Tyr hydrogels with DMT. Taken together, the injectable HA–Tyr hydrogels were thought suitable to be developed as a therapeutically effective drug carrier for the treatment of RA.