Edaravone-Loaded Alginate-Based Nanocomposite Hydrogel Accelerated Chronic Wound Healing in Diabetic Mice

Refractory wound healing is one of the most common complications of diabetes. Excessive production of reactive oxygen species (ROS) can cause chronic inflammation and thus impair cutaneous wound healing. Scavenging these ROS in wound dressing may offer effective treatment for chronic wounds. Here, a nanocomposite hydrogel based on alginate and positively charged Eudragit nanoparticles containing edaravone, an efficient free radical scavenger, was developed for maximal ROS sequestration. Eudragit nanoparticles enhanced edaravone solubility and stability breaking the limitations in application. Furthermore, loading these Eudragit nanoparticles into an alginate hydrogel increased the protection and sustained the release of edaravone. The nanocomposite hydrogel is shown to promote wound healing in a dose-dependent way. A low dose of edaravone-loaded nanocomposite hydrogel accelerated wound healing in diabetic mice. On the contrary, a high dose of edaravone might hamper the healing. Those results indicated the dual role of ROS in chronic wounds. In addition, the discovery of this work pointed out that dose could be the key factor limiting the translational application of antioxidants in wound healing.