Protective effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide)- loaded polymeric micelles against neurotoxicity in spinal cord: In vitro

Abstract

The incidence and prevalence of spinal cord injury (SCI) as a high disabling injury have enc ouraged the researchers to find some therapeutic strategies. The spinal cord is highly sensitive to oxidative stress and maintaining homeostasis is essential for redox status in neurons. Therefore, in this study. On the other hand, the application of drugs can induce some unwanted effects on the viability of neurons. Therefore, in this study, 1,2-benzisoxazole-3-methanesulfonamide (zonisamide) as a second-generation antiepileptic drug was formulated by micelles and characterized by TEM and DLS techniques. Afterward the protective effects of 1,2-benzisoxazole-3-methanesulfonamide-loaded micelles against stimulated oxidative stress and cytotoxicity were assessed by MTT, ROS, staining and enzyme activity assays. It was shown that the fabricated 1,2-benzisoxazole-3-methanesulfonamide-loaded micelles with a size of about 60–90 nm have a good colloidal stability and show a sustained drug release at physiological pH. Furthermore, it was determined that the neuroprotective effects of 1,2-benzisoxazole-3-methanesulfonamide-loaded micelles against cytotoxicity, ROS production, morphological changes, caspase-3 activation triggered by H2O2 was more pronounced than non-formulated drug. In conclusion, this study may provide useful information regarding the advancement of therapeutic approach for treatment of SCI.