Injectable anti-inflammatory supramolecular nanofiber hydrogel to promote ranibizumab therapy in age-related macular degeneration treatment

The exact pathogenesis of age-related macular degeneration (AMD) leading to visual impairment and severe vision loss is still unclear, and the currently available treatments are often unsatisfactory. Previous studies have demonstrated both oxidative stress-induced damage to the retinal pigment epithelium (RPE) and inflammation are involved in AMD. Although anti-vascular endothelial growth factor (VEGF) therapy can impair the growth of new blood vessels, serious side effects were found with repeated monthly intravitreal injections. Here, an injectable hydrogel based on an anti-inflammatory betamethasone phosphate (BetP) drug (BetP-Gel) was designed to enable long-term efficient release of ranibizumab (RZB) to attenuate choroidal neovascularization (CNV), reduce vascular leakage and inhibit vascular proliferation in the retina, which significantly increased the effective treatment time of ranibizumab compared with that in clinical practice. In particular, experimental data with in vitro and in vivo models revealed that BetP-Gel itself had a strong ability to scavenge intracellular reactive oxygen species (ROS) and reduce tumour necrosis factor-a (TNF-a) as well as interleukin (IL-1ß, IL-6, IL-8, and IL-18) inflammatory cytokines, inhibiting ROS- and inflammation-induced retinal damage. Altogether, the carrier-free system (RZB@BetP-Gel) could serve as a novel antioxidant, anti-inflammatory and anti-neovascularization agent for the treatment of AMD. Overall design: BetP-Gel promote ranibizumab therapy in age-related macular degeneration treatment