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

Abstract

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.

Functional Biomaterials for Treatment of Chronic Wound

“…Edaravone, a commercial drug with the ability to scavenge •OH, is used to treat cerebral ischemia and has also been used in chronic wounds. The therapeutic effect was dosedependent, which proved the dual role of ROS in chronic wound healing (Fan et al, 2019). Ceria have also attracted attention as potential treatments for excessive-ROS-related diseases owing to their ability to mimic the activity of multiple antioxidant enzymes.…”

“…It has been proven that biomaterials and bioactive agents with antioxidative function, including diol-citrate esters, edaravone, and cerium dioxide, can accelerate chronic wound healing (Luo et al, 2004;Zhu et al, 2016;Speidel et al, 2017;Fan et al, 2019;Wu et al, 2019).…”

Shixiang Plaster, a Traditional Chinese Medicine, Promotes Healing in a Rat Model of Diabetic Ulcer Through the receptor for Advanced Glycation End Products (RAGE)/Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF)/Vascular Cell Adhesion Molecule-1 (VCAM-1)/Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathways

“…Delayed healing of skin ulcers is a complication of DM that is caused by diabetic microvascular disease and results in the failure of complete healing of skin wounds resulting in chronic ulcers, particularly in the lower limb [6]. Wound healing, or tissue repair, is a complex physiological process and involves several phases that include inflammation, cell proliferation, fibrosis, and remodeling that all depend on angiogenesis, which is the hallmark of granulation tissue [7].…”

Effects of Edaravone on Neurological Function and Tumor Necrosis Factor Alpha and Interleukin 8 Levels in Patients with Cerebral Infarction

“…It exists in the form of edaravone anion and can transfer electrons to oxygen-free radicals, thereby transforming free radicals into edaravone-free radicals [18]. In addition, it can inhibit peroxidation induced by lipid-and water-soluble peroxy radicals [19]. Various animal models have revealed that edaravone has neuroprotective effects [20].…”