In Situ Forming Hydrogel as a Tracer and Degradable Lacrimal Plug for Dry Eye Treatment.

Lacrimal plug is an effective and widely therapeutic strategy to treat dry eye. However, almost all commercialized plugs are fixed in a certain design and associated with many complications, such as spontaneous plug extrusion, epiphora, and granuloma and cannot be traced in the long-term. Herein, a simple in situ forming hydrogel is developed as a tracer and degradable lacrimal plug to achieve the best match with the irregular lacrimal passages. In this strategy, methacrylate-modified silk fibroin (SFMA) is served as a network, and a self-assembled indocyanine green fluorescence tracer nanoparticle (FTN) is embedded as an indicator to develop the hydrogel plug using visible photo-crosslinking. This SFMA/FTN hydrogel plug has excellent biocompatibility and biodegradability, which can be noninvasively monitored by near-infrared light. In vivo tests based on dry eye rabbits show that the SFMA/FTN hydrogel plug can completely block the lacrimal passages and greatly improve the various clinical indicators of dry eye. These results demonstrate that the SFMA/FTN hydrogel is suitable as an injectable and degradable lacrimal plug with a long-term tracking function. The work offers a new approach to the development of absorbable plugs for the treatment of dry eye.

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye.

The inflammatory response mediated by oxidative stress is the main pathogenesis of dry eye, but clinical observations have shown that scavenging oxygen-free radicals alone has limited therapeutic effect. Moreover, the unique anatomy and physiology of the ocular surface result in low bioavailability of drugs, and higher concentration is required to achieve the desired efficacy, which, however, may bring systemic side effects. These problems pose a challenge, but the revelation of the ROS-NLRP3-IL-1ß signaling axis opens up new possibilities. In this investigation, an NLRP3 inhibitor was successfully encapsulated in polydopamine-based microgels and used for dry eye treatment. It was demonstrated that the well-designed microgels exhibited good biocompatibility, prolonged drug retention time on the ocular surface, and effective inhibition of corneal epithelial damage and cell apoptosis. In addition, due to the synergistic effect, the NLRP3 inhibitor-loaded microgels could exert enhanced oxygen radical scavenging and inflammation-inhibiting effects at a lower dose than monotherapy. These findings suggest that polydopamine-based microgels have advantages as ocular surface drug delivery platforms and have promising applications in oxidative damage-related inflammatory diseases in synergy with anti-inflammatory drugs.