Abstract:
Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.
摘要:
提高抗癫痫药物进入大脑的效率是降低其外周毒性的关键。鼻内给药和纳米药物的组合提供了一种通过绕过血脑屏障治疗癫痫发作的实用方法。在这项研究中,通过共沉淀-水热法制备了载有苯妥英(PHT)的层状双氢氧化物纳米颗粒(BSA-LDHs-PHT),用于控制癫痫发作。在这项研究中,阐述了BSA-LDHs-PHT的制备方法和表征。体外药物释放实验表明,BSA-LDHs-PHT的药物释放速度快、持续,这对于急性癫痫发作控制和慢性癫痫治疗至关重要。鼻内给药后的体内生物分布测定表明BSA-LDH具有优异的脑靶向能力。与BSA-Cyanine5.5相比,BSA-LDHs-Cyanine5.5在所有测试时间点中与更高的脑/外周比率相关。用小剂量的BSA-LDHs-PHT鼻内给药后,戊四唑诱导的小鼠模型的癫痫发作潜伏期得到有效改善。总的来说,本研究成功设计并应用了BSA-LDHs-PHT作为一种有希望的治疗癫痫发作的策略,并提高了治疗效果.