DataSheet1_Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye.docx

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-1β 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.

氧化应激介导的炎症反应是干眼症的主要发病机制，但临床观察显示，仅清除氧自由基的治疗效果有限。此外，眼表独特的解剖与生理特征导致药物生物利用度较低，需达到更高浓度方可实现预期疗效，然而这可能引发全身不良反应。上述问题为干眼症的临床治疗带来了挑战，但活性氧（ROS）-NLRP3-IL-1β信号轴的研究发现为其开辟了新的可能性。本研究成功将NLRP3抑制剂封装于聚多巴胺基微凝胶中，用于干眼症的治疗。研究证实，该精心设计的微凝胶具备良好的生物相容性，可延长药物在眼表的滞留时间，并能有效抑制角膜上皮损伤与细胞凋亡。此外，得益于协同效应，负载NLRP3抑制剂的微凝胶在更低剂量下，即可发挥比单一疗法更强的氧自由基清除与炎症抑制作用。上述研究结果表明，聚多巴胺基微凝胶作为眼表药物递送平台具有显著优势，且与抗炎药物联用时，在氧化损伤相关炎症性疾病中拥有良好的应用前景。