Recent advances in the polysaccharide nanogel design for dry eye therapy.

Dry eye disease (DED) is a multifactorial disorder of ocular surface marked by tear film instability, hyperosmolarity, inflammation, and epithelial damage. Current therapies, such as artificial tears and topical anti-inflammatory agents, often provide only temporary relief because of rapid tear turnover, low bioavailability, and frequent dosing requirements. Polysaccharide-based nanogels have gained increasing attention as advanced ocular delivery systems because they combine high water retention, intrinsic biocompatibility, mucoadhesive behavior, prolonged precorneal residence, and sustained drug release. This review summarizes recent progress in the design and application of polysaccharide nanogels for DED, linking disease pathophysiology with material selection, fabrication strategies, and therapeutic mechanisms. Emphasis is placed on stimuli-responsive and multifunctional nanogels that respond to pH, temperature, enzymes, or ionic strength to enhance retention, improve drug penetration, and reduce dosing frequency. Finally, key challenges related to manufacturing scalability, long-term ocular safety, regulatory considerations, and clinical translation are critically evaluated. Specifically, technical barriers such as sterilization of nanoscale systems, control of particle size distribution, prevention of aggregation during storage, and batch-to-batch variability in crosslinking density are discussed, along with emerging scalable solutions. Overall, this review highlights polysaccharide-based nanogels as promising, patient-friendly biomaterials and guides the rational development of next-generation therapies for DED management.