Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.