Dry eye disease (DED) remains a significant challenge in effective drug delivery due to rapid precorneal clearance and suboptimal concentration control, leading to frequent dosing and poor patient compliance. Herein, we developed mucoadhesive phenylboronic acid-modified alginate microcarriers using a microfluidic electrospray strategy for sustained diquafosol tetrasodium (DQS) release and prolonged ocular surface retention.The designed phenylboronic acid-modified alginate polymer enabled both mucoadhesion via dynamic boronate ester bonds to the corneal surface and controllable drug release through interactions with the cis-diol groups in DQS. In a hyperosmolarity-induced human corneal epithelial cell model, the microcarriers demonstrated excellent biocompatibility and effectively protected human corneal epithelial cells from hyperosmotic stress by reducing intracellular ROS accumulation and suppressing inflammatory responses. Furthermore, in a benzalkonium chloride-induced murine DED model, the microcarrier-based eye drops effectively restored corneal epithelial integrity, improved tear production, and alleviated histological signs of ocular surface damage. These results indicated that our drug-loaded, mucoadhesive microcarrier system represents a promising and potent platform for advanced DED therapy, offering the potential for improved clinical outcomes.

Bacterial keratitis is a leading cause of corneal blindness, yet current antibiotic therapies suffer from poor ocular bioavailability and rising drug resistance. Effective treatment requires not only bacterial eradication but also coordinated anti-inflammation and wound repair. In this paper, we present a "two birds with one stone" strategy for bacterial keratitis treatment based on an ultrasound-activated cascade responsive core-shell microneedle. Upon corneal insertion and ultrasound stimulation, piezoelectric nanoparticles embedded in the microneedle shell generate reactive oxygen species (ROS) to eliminate bacteria. The elevated ROS levels subsequently trigger the degradation of an ROS-responsive hydrogel core, enabling sustained release of mesenchymal stem cell derived exosomes (MSC-Exos) that neutralize residual oxidative stress, promote macrophage M1 to M2 polarization, and facilitate epithelial barrier restoration. Our proposed formulation demonstrated enhanced therapeutic efficacy in a rat keratitis model, outperforming conventional antibiotic eye drops in bacterial clearance, inflammation resolution, and corneal repair. These findings establish the cascade-responsive core-shell microneedles as a clinically promising strategy for treating bacterial keratitis and other infectious ocular diseases.