Purpose: The current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS).
Methods: ZMT-SNEDDS were fabricated based on full factorial design (3²) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out.
Results: Upon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59± 0.17 nm with narrow size distribution, zeta potential (− 23.5± 1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination.
Conclusion: In a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution.

Keywords: ZMT-SNEDDS, acute migraine, real-time monitoring, nitroglycerin, activity cage, algesia

中文翻译：

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佐米曲坦在新型自纳米乳化给药系统中的潜在协同作用：ATR-FTIR 实时快速溶出监测和药效学评估

目的：目前的工作旨在克服佐米曲坦（ZMT）的渗透性差和不良副作用，并通过利用薰衣草精油的协同作用来制备ZMT自纳米乳化药物，以提高其治疗急性偏头痛的疗效。交付系统（ZMT-SNEDDS）。
方法： ZMT-SNEDDS 基于全因子设计（3 ²) 以统计评估油和表面活性剂浓度对纳米乳液球大小、zeta 电位和药物溶出效率百分比的影响。开发并验证了一种 ATR-FTIR 方法，用于连续实时监测 ZMT 溶解和渗透。疗效研究中使用的优化 ZMT-SNEDDS 的剂量是根据急性毒性研究选择的。对硝酸甘油诱导的偏头痛大鼠进行疗效研究，并通过活动笼和热试验、脑电图、电惊厥刺激和脑组织生化分析进行评价。最后，进行了大脑的组织病理学和免疫组织化学检查。
结果：稀释后，优化的 ZMT-SNEDDS (F5) 呈现出 19.59±0.17 nm 的纳米级球形液滴，具有窄尺寸分布、zeta 电位 (- 23.5± 1.17mV) 和快速乳化特性。ATR-FTIR 光谱阐明了溶解和渗透的完整时间过程，证实了 F5 的卓越性能。此外，ZMT-SNEDDS (F5) 在急性毒性研究中显示出安全性。与ZMT溶液相比，F5衍生的大鼠脑组织中ZMT浓度较低，但其对心理状态、镇痛、维持正常脑电活动和延迟惊厥的作用较好。它抵消了硝酸甘油诱导的脑生化变化，这已通过组织病理学检查得到证实。
结论：简而言之，与传统的佐米曲坦溶液相比，这些发现证实了基于薰衣草油的 ZMT-SNEDDS 在偏头痛治疗中的显着协同功效和高效力。

关键词： ZMT-SNEDDS，急性偏头痛，实时监测，硝酸甘油，活动笼，痛觉