Ultrasound-responsive hydrogel microcarriers co-loading dexamethasone and urate oxidase for localized gout management.

Introduction: Gouty arthritis is characterized by the deposition of monosodium urate crystals, which drive not only joint inflammation but also progressive bone erosion and structural damage. Existing therapeutic strategies remain limited by poor local bioavailability and inadequate protection of bone tissue. Hydrogel drug delivery systems offer significant potential for localized gout therapy. However, the co-delivery of anti-inflammatory and urate-lowering agents using hydrogel platforms remains largely unexplored. Methods: In this study, we propose a novel ultrasound-responsive hydrogel microcarrier (DXM/UOX@MPs) fabricated via microfluidic electrospray, composed of a sodium alginate/N-isopropylacrylamide (NIPAM) double network and co-loaded with dexamethasone (DXM) and urate oxidase (UOX). The microcarriers were designed to be administered intra-articularly and evaluated in gouty rat models. Mechanistically, DXM is slowly released for long-term anti-inflammation, while high-frequency ultrasound triggers NIPAM contraction to release UOX for targeted uric acid degradation. Results: In gouty rat models, combined therapy with DXM/UOX@MPs and ultrasound achieved superior efficacy. We observed a significant reduction in joint swelling and inflammation in the affected joints. Furthermore, combining the treatment with the inherent cartilage-protective properties of the hydrogel matrix offered a strong protective effect that successfully safeguarded both cartilage and bone from damage. Discussion: This synergistic strategy addresses key clinical drawbacks, such as poor local bioavailability and inadequate bone tissue protection. By effectively combining sustained anti-inflammation and ultrasound-triggered uric acid degradation, it provides a promising therapeutic approach for gout with high clinical application value.