Gouty Arthritic Microenvironment Triggered Core–Shell Microneedles for Hydrogen‐Enzyme Synergistic Gout Therapy

Gouty arthritis (GA) is a chronic and progressive disease generally characterized by high articular uric acid (UA) levels and an inflammatory immune microenvironment. Clinical data show that UA reduction therapy or anti‐inflammation alone usually provides unsatisfactory efficacy. Herein, we propose a GA microenvironment triggered core–shell microneedle as a transdermal drug delivery system to provide a hydrogen‐enzyme synergistic therapeutic strategy for GA management. Polydimethylsiloxane inversion molding and subsequent polymer coating are used to fabricate core–shell microneedle, which employs uricase‐loaded hyaluronic acid as the core for UA degradation, while ammonia borane‐encapsulated mesoporous silica nanoparticles from poly(lactic‐co‐glycolic) copolymers shell for anti‐inflammatory therapy. Upon pressing microneedle onto the joint, acidic GA microenvironment first triggers the efficient hydrogen release from the loaded ammonia borane in shell, thus selectively scavenging reactive oxygen species and effectively neutralizing proinflammatory factors. Uricase from microneedle core continues to catalyze the degradation of articular UA and lowers UA to normal levels. Both acute and chronic gout models are established to demonstrate the robust therapeutic effect of the core–shell microneedle. Via synergistic hydrogen‐enzyme therapy, the core–shell microneedle possesses considerable clinical translation potential in gout management.