Mucoadhesive polymeric microcarriers delivering diquafosol tetrasodium for dry eye therapy

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.