Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor β (TGFβ) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFβ inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1 (as those levels found in patients' synovial fluid). A monthly injection strategy was then designed of using poly lactic-