Chitosan-Functionalized Liposome-Mediated Fundus Delivery of Epigallocatechin-3-Gallate for Diabetic Retinopathy Therapy.

Abstract

Among working-age adults in the contemporary era, more than 30% of individuals with diabetes are at risk of developing diabetic retinopathy (DR), a progressive ocular disorder that is the leading cause of visual impairment and blindness. 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-modified liposomes encapsulating epigallocatechin-3-gallate (EGCG), capable of transporting EGCG from the ocular surface to the retina. Mechanistic studies revealed that efficient retinal delivery of EGCG could protect Müller cells against high glucose (HG)-induced injury via SIRT1-BNIP3-mediated mitophagy. In vivo, the developed EGCG@CS-LIP 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-LIP 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-LIP indicated the excellent ocular biocompatibility, highlighting its promise for future clinical translation in DR therapy.