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Despite its high prevalence, treatment options remain limited. Current therapeutic strategies only focus on the inhibition of neovascularization or prevention of vascular leakage. Additionally, the majority of conventional eye drop formulations fail to deliver drugs efficiently to the retina, further limiting clinical applicability. To address these issues, we herein designed and developed an eye drop formulation based on the chitosan\u2010modified liposomes encapsulating epigallocatechin\u20103\u2010gallate (EGCG), capable of transporting EGCG from the ocular surface to the retina. Mechanistic studies revealed that efficient retinal delivery of EGCG could protect M\u00fcller cells against high glucose (HG)\u2010induced injury via SIRT1\u2010BNIP3\u2010mediated mitophagy. In vivo, the developed EGCG@CS\u2010LIP showed enhanced fundus delivery and therapeutic efficacy compared with conventional liposomes or free EGCG systems, attributed to the transient modulation of corneal tight junctions. More importantly, the EGCG@CS\u2010LIP eye drops could effectively increase the expression level of SIRT1 protein and inhibit the apoptosis and damage in retina, thus exerting significant in vivo therapeutic effects for the effective treatments of DR. Lastly, the constructed EGCG@CS\u2010LIP indicated the excellent ocular biocompatibility, highlighting its promise for future clinical translation in DR therapy.<\/jats:p>","DOI":"10.1002\/adhm.202505083","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:26:54Z","timestamp":1781324814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chitosan\u2010Functionalized Liposome\u2010Mediated Fundus Delivery of Epigallocatechin\u20103\u2010Gallate for Diabetic Retinopathy Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Xingxiu","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Fourth Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoliang","family":"Shi","sequence":"additional","affiliation":[{"name":"Suzhou Key Laboratory of Nanotechnology and 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