Nutraceutical emulsion containing valproic acid (NE-VPA): a drug delivery system for reversion of seizures in zebrafish larvae epilepsy model
Nutraceutical emulsion containing valproic acid (NE-VPA): a drug delivery system for reversion of seizures in zebrafish larvae epilepsy model
复制标题
DOI：
10.1007/s40005-017-0316-x
复制
发表时间：
2017-09-01
影响因子：
5.5
通讯作者：
Jimena Prieto, Maria
中科院分区：
文献类型：
--
作者：
Agustina Feas, Daniela;Edith Igartua, Daniela;Jimena Prieto, Maria
丙戊酸（VPA）是一种抗癫痫药，目前用于神经退行性疾病。但是，需要高剂量才能获得治疗作用。长链多不饱和脂肪酸（PUFA），例如欧米茄3和欧米茄6，是神经疾病治疗的有效补充。先前的研究报告说，含有PUFA的饮食补充剂以及抗癫痫药的给药可显着降低癫痫发作的频率。基于此，这项工作的主要目标是基于在油/水（O/W）营养乳液（NE）中基于VPA封装的复合物，该营养乳液（NE）富含PUFAS进行口服给药。此外，VPA的封装可能会减少其剂量并增加其治疗作用。为了研究其效果，我们使用了斑马鱼幼虫模型的诱导性癫痫行为行为模型，并使用了螺旋形药物戊酸药物（PTZ）。结果表明，当在NE（NE-VPA）中合并100 mu M VPA和脂肪酸时，PTZ处理的斑马鱼幼虫的癫痫样行为显着降低。此外，还研究了形态变化，肝毒性，致死性和心率。尽管高剂量的VPA发挥了心脏毒性作用，但在NE中添加了这种药物后，它不再被发现。这种治疗作用产生了显着的抗癫痫作用，并未导致剧毒或致命作用。为了开发改进的药物治疗，考虑到所有使用的组件均已批准用于食用FDA，因此所选的NE-VPA很容易被纳入临床试验中。
Valproic acid (VPA) is an antiepileptic drug, which is currently used in neurodegenerative diseases. However, a high dose is required to obtain a therapeutic effect. Long-chain polyunsaturated fatty acids (PUFAs), such as omega 3 and omega 6, are efficient complements in treatments for neurological diseases. Previous studies have reported that a dietary supplement containing PUFAs together with the administration of antiepileptic drugs significantly reduces the frequency of seizures. Based on this, the main goal of this work was to obtain a complex based on VPA encapsulation in an oil/water (o/w) nutraceutical emulsion (NE) enriched with PUFAs for oral administration. Besides, encapsulation of VPA might reduce its dose and increase its therapeutic effect. In order to study its effect, we used a zebrafish larvae model of induced epileptiform behavior with the proconvulsant drug pentylenetetrazol (PTZ). Results have shown that when 100 mu M VPA and fatty acids were combined in the NE (NE-VPA), the epileptiform behavior of PTZ-treated zebrafish larvae decreased significantly. Additionally, morphological changes, hepatotoxicity, lethality and heart rate were studied. Despite the fact that a high dose of VPA exerted a cardiotoxic effect, this was no longer detected after addition of this drug in the NE. This treatment exerted a significant antiepileptic effect and did not result in highly toxic or lethal effects. In order to develop an improved pharmaceutical treatment, and considering that all the components used are FDA approved for consumption, the NE-VPA selected might be easily incorporated into clinical trials.