Urate-responsive hydrogel microneedles with rapid bubble separation for simplified long-term gout management.

Gout is a chronic inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints and other areas, and the MSU crystals is a result of the progressive long-term hyperuricemia. Therefore, long-term gout management requires a combination of on-demand urate lowering therapy and anti-inflammatory treatment. And the long-term combined administration urgently requires a simplified and effective administration method. Here, we developed a smart hydrogel microneedle system featuring urate-responsive drug release and rapid bubble separation. This system utilized the rapid bubble separation to retain the hydrogel drug reservoir that simultaneously carried the urate lowering drug uricase and the anti-inflammatory drug colchicine in the skin. In hyperuricemia, the ROS-responsive hydrogel formed by the spontaneous cross-linking of dopamine-modified β-cyclodextrin, polyvinyl alcohol and phenylboric acid linker was promoted for degradation by the H2O2 released from the decomposition of uric acid by uricase, thereby achieving the urate-responsive release. In addition, colchicine loading was increased by forming inclusion complexes with dopamine-modified β-cyclodextrin. Thus, this smart microneedle system retained the drug reservoir with urate-responsive release in the skin through transdermal delivery. It not only dynamically controlled the uric acid concentration and decomposed MSU crystals, but also has a powerful real-time anti-inflammatory effect on gout flares. Accordingly, we believe the smart microneedle system has great potential for long-term gout management.