DNA Supramolecular Hydrogel-Enabled Sustained Delivery of Metformin for Relieving Osteoarthritis.

Osteoarthritis (OA) is a musculoskeletal disorder affecting ∼500 million people worldwide. Metformin (MET), as an oral hypoglycemic drug approved by the Food and Drug Administration, has displayed promising potential for treating OA. Nonetheless, in the articular cavity, MET suffers from rapid clearance and cannot circumvent the severe inflammatory environment, greatly confining the therapeutic efficacy. Herein, DNA supramolecular hydrogel (DSH) has been utilized as a sustained drug delivery vehicle for MET to treat OA, which dramatically prolonged the retention time of MET in the articular cavity from 3 to 14 days and simultaneously exerted a greater anti-inflammatory effect. Our delivery platform, termed MET@DSH, better protects cartilage than single-agent MET. Additionally, the corresponding molecular mechanisms underlying the therapeutic effects were also analyzed. We anticipate this DNA supramolecular hydrogel-enabled sustained drug delivery and anti-inflammatory strategy will reshape the current landscape of OA treatment.