Hydrogel-encapsulated antioxidant nanotherapeutics against age-related macular degeneration (AMD) oxidative damage

Age-related macular degeneration (AMD) is still the main cause of irreversible vision loss, and the current intravitreal injections is limited by frequent administration and short retinal residence time. This review summarizes the latest progress of hydrogel-nanocarrier hybrid systems, aiming at prolonging ophthalmic drug delivery and supporting retinal tissue. We summarized the pathogenesis of AMD, focusing on oxidative stress and degeneration of retinal pigment epithelium (RPE), and investigated inorganic and organic nano-platforms endowed with antioxidant, anti-inflammatory and anti-angiogenesis functions. The design strategy of embedding nanoparticles into injectable or stimulus-responsive hydrogels is discussed. However, challenges remain, including long-term biocompatibility, inflammatory response to degradation products and potential tissue accumulation. Finally, it is emphasized to accelerate clinical translation through comprehensive long-term in vivo safety evaluation, quantitative optimization of release kinetics, standardized evaluation scheme and development of extensible manufacturing process. It is worth noting that this review mainly emphasizes inorganic nanoparticles and extracellular vesicles, but does not discuss other mature organic nanocarriers in detail. These carriers have been widely studied and emphasized by many other reviews.