Mucoadhesive and ROS-responsive polymeric vesicles for anti-angiogenic therapy in corneal neovascularization

Corneal neovascularization (CNV) is a major cause of visual impairment worldwide and results from disruption of the cornea's angiogenic privilege by excessive angiogenic signaling and oxidative stress. Current clinical management relies on corticosteroids, nonsteroidal anti-inflammatory drugs, or anti-VEGF injections, yet these approaches often provide incomplete efficacy and are associated with adverse effects, invasiveness, or limited patient compliance. In this study, we developed a multifunctional polymeric vesicle platform, termed PPM, to address these limitations through combined anti-angiogenic and antioxidant mechanisms. PPM vesicles are self-assembled from the diblock copolymer P(PEGMA₁₀-co-PBA₂)-b-PMTEMA₂₅, in which the PMTEMA membrane confers reactive oxygen species (ROS) responsiveness and intrinsic antioxidative capacity, while the phenylboronic acid-functionalized PEGMA corona enhances mucoadhesion. The multi-target tyrosine kinase inhibitor nintedanib (Nint) was encapsulated within the hydrophobic vesicle membrane, enabling controlled release under ROS-rich inflammatory conditions. In a murine CNV model, topically administered Nint@PPM vesicles suppressed pathological neovascularization, attenuated oxidative stress, and facilitated corneal epithelial recovery. These results demonstrate that ROS-responsive, mucoadhesive polymeric vesicles provide a noninvasive strategy for improving ocular drug delivery and CNV treatment.