Development of a ROS-responsive, glutathione-functionalized injectable hydrogel system for controlled drug release

Oxidative stress arises from an imbalance between excessive production of reactive oxygen species (ROS) and the body’s antioxidant defenses. In neurodegenerative diseases, this imbalance leads to ROS accumulation, causing neuronal dysfunction and cell death. Traditional drug therapies often fail to address the dynamic nature of neuroinflammation, limiting their therapeutic efficacy. To overcome this challenge, we have developed an innovative ROS-responsive injectable hydrogel. This hydrogel is designed to detect oxidative stress sensitively and release glutathione in a controlled manner, thereby modulating inflammation and restoring the damaged immune microenvironment to facilitate tissue repair. The hydrogel was synthesized by crosslinking polyvinyl alcohol (PVA) with sodium alginate modified with 3-aminophenylboronic acid (Alg-PBA). We investigated the hydrogel’s formation mechanism and analyzed how component variations affect its morphological and rheological properties. Our findings demonstrate that an optimal Alg-PBA to PVA weight ratio of 2:1 yields a hydrogel with superior mechanical strength. Glutathione (GSH) release studies confirmed the hydrogel’s pronounced ROS-responsive drug release behavior. Furthermore, biocompatibility assessments revealed that the hydrogel loaded with 100 μg/mL GSH exhibited excellent compatibility and significantly inhibited neuronal apoptosis under oxygen-glucose deprivation (OGD) conditions. This work presents a promising strategy for treating inflammation-related diseases and provides valuable insights for designing next-generation hydrogels that adapt to injury-responsive microenvironments.