Guler Ece, Yekeler Humeyra B, Ozdemir Kumral Zarife N, Parviz Gita, Ozcan Gul S, Uner Burcu, Demirbas Sinem G, Ayyildiz Simge, Yazir Yusufhan, Kalaskar Deepak, Cam Muhammet E
Department of Pharmacology, Faculty of Pharmacy, Istanbul Kent University, Istanbul 34406, Türkiye.
Center for Nanotechnology and Biomaterials Application and Research, Marmara University, Istanbul 34890, Türkiye.
ACS Biomater Sci Eng. 2025 Mar 10;11(3):1523-1538. doi: 10.1021/acsbiomaterials.4c02294. Epub 2024 Dec 21.
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 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 via pentylenetetrazole kindled-induced animal modeling. The parameter of 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.
癫痫是人类发现的最古老的神经系统疾病之一。这种疾病与无法抑制的神经电脉冲刺激引发的无端癫痫发作紧密相关。口服丙戊酸盐类药物已被用于预防性治疗；然而，口服给药不适用于危急情况，因此需要满足即时神经支配需求的给药途径。为了解决这一缺点，开发了包裹在聚环氧乙烷/聚乙烯吡咯烷酮（PEO/PVP）纳米纤维贴片中的丙戊酸钠，旨在实现舌下给药。最初，通过中心复合设计（CCD）对生产工艺进行了设计和优化。采用新型设备通过加压旋转法完成纳米纤维的制备。对制备的生物材料进行化学、空间和热性能检测。通过扫描电子显微镜从形态学上证明了原始和浸渍纳米纤维贴片均无豆状且外观均匀。此外，充分口腔分散的浸渍贴片在一分钟内释放了超过90%的药物含量。通过对SH-SY5Y神经母细胞瘤细胞进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四氮唑溴盐（MTT）测定获得细胞安全性保证后，通过戊四氮点燃诱导的动物模型证实了浸渍贴片的抗癫痫保护作用。行为评估的参数是拉辛评分系统。此外，通过荧光染色突出显示了不同测试组之间检测到的组织病理学差异。最后，根据丙二醛、谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平的定量变化确定氧化应激。本文的总体结论表明，负载丙戊酸钠的PEO/PVP纳米纤维贴片显著预防了戊四氮引起的行为、结构和氧化损伤。
