Fabrication of oro-dispersible sodium valproate loaded nanofibrous patches for immediate epileptic innervation

Abstract

Epilepsy is one of the oldest neurological disorders discovered by mankind. This condition is firmly coupled with unprovoked seizures stimulated by irrepressible neuroelectrical blasts. Orally taken valproate family has been employed for prophylactic management; however, oral administration is not applicable for critical scenarios, thus calling for medication routes fulfilling necessities of immediate innervation. In order to address this shortcoming, sodium valproate entrapped in poly(ethylene oxide)/polyvinylpyrrolidone (PEO/PVP) nanofibrous patches was developed with the aim of sublingual drug delivery. Initially, the production process was designed and optimized via the central composite design (CCD). Nanofiber fabrication was accomplished with a novel device by using the pressurized gyration method. Fabricated biomaterials were chemically, spatially, and thermally inspected. The beanless and homogeneous appearance of both virgin and impregnated nanofibrous patches was morphologically demonstrated via scanning electron microscopy. Additionally, adequately oro-dispersed impregnated patches released more than 90% of their drug content in under a minute. Following in vitro cyto-safety assurance acquired through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on SH-SY5Y neuroblastoma cells, the protective antiepileptic effect of impregnated patches was affirmed in vivo via pentylenetetrazole kindled-induced Mus musculus animal modeling. The parameter of in vivo behavioral evaluation was the Racine scoring system. Moreover, histopathological distinctions detected between different test groups were highlighted via fluorescence staining. Finally, the oxidative stress was determined according to quantitative variations of malondialdehyde, glutathione, superoxide dismutase, and catalase levels. The overall conclusion herein suggests that sodium valproate-loaded PEO/PVP nanofibrous patches strikingly prevented behavioral, structural, and oxidative deteriorations caused by pentylenetetrazole.