ROS-Responsive Hydrogel for Localized Neurotrophic Delivery and Oxidative Stress Modulation in Alzheimer’s Disease

Background: Neuroinflammation and oxidative stress are key features of Alzheimer's disease (AD), offering potential targets for localized therapeutic intervention.Delivering neurotrophic factors specifically to inflamed brain regions could improve treatment efficacy while minimizing systemic exposure.Methods: We developed a reactive oxygen species (ROS)-responsive hydrogel incorporating oxidation-labile linkers to enable the on-demand release of brain-derived neurotrophic factor (BDNF).The hydrogel's porous structure was characterized via Scanning Electron Microscopy (SEM), and drug release behavior was evaluated under oxidative and physiological conditions.Cytoprotective efficacy was tested in H 2 O 2 -treated PC12 cells.Results: The hydrogel exhibited high porosity and released BDNF rapidly in oxidative environments, with minimal release under normal conditions.It reduced intracellular ROS in stressed PC12 cells.Conclusion: This ROS-responsive hydrogel serves as a biocompatible and intelligent drug delivery system with potential for targeted oxidative stress modulation and neurotrophic support in the treatment of AD.