Confined antisolvent precipitation enables efficient drug encapsulation in microgels for effective gouty arthritis therapy

Microgels are attractive carriers for local drug delivery, but the poor compatibility of hydrophobic drugs with hydrophilic networks limits drug loading and causes uncontrolled release. Here, we present a microfluidic-assisted confined antisolvent precipitation strategy that enables broadly applicable and efficient encapsulation of poorly soluble drugs inside microgels. Rapid solvent exchange inside microfluidic droplets triggers in situ supersaturation and crystallization of hydrophobic drugs before microgel gelation, creating a drug crystalline retention effect that stabilizes drug domains across gelling hydrophilic polymer networks. This mechanism not only enhances drug loading but also mitigates burst release. Importantly, the strategy is applicable to diverse hydrophilic polymer systems capable of rapid gelation, as shown by successful encapsulation of multiple hydrophobic drugs in both natural and synthetic microgels. Compared with conventional methods, the resulting drug-loaded microgels achieved over fivefold higher loading while maintaining a favorable morphology. To further strengthen drug–matrix interactions, tryptophan-grafted chitosan was developed, extending curcumin release for over three days. In a mouse gouty arthritis model, curcumin-loaded microgels enabled rapid suppression of anti-inflammatory cytokines, sustained immunomodulation, and functional joint recovery. Overall, this work establishes a broadly applicable platform for fabricating high-loading, long-acting microgels for the treatment of inflammatory and degenerative diseases. This study presents a microgel-based drug delivery system developed through a confined antisolvent precipitation strategy to efficiently encapsulate poorly soluble drugs. The resulting microgels provide high drug loading and sustained release. In a mouse gouty arthritis model, this approach reduced inflammation and restored joint function, offering a promising platform for localized treatment of inflammatory and degenerative diseases. • Confined antisolvent precipitation enables high drug loading in microgels • In situ crystallization forms stable drug domains and prevents burst release • Matrix-independent approach applies to natural and synthetic microgels • Sustained release alleviates inflammation and restores joint function in mice