Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Department of Hematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital & Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu 610072, China.
Int J Pharm. 2020 Sep 25;587:119724. doi: 10.1016/j.ijpharm.2020.119724. Epub 2020 Aug 2.
The purpose of this study was to develop an injectable submicron emulsion of eugenol (Eug-SE) and to investigate its antagonism on epilepsy. The formulation was optimized using a complete randomized design, comprising 5% (w/v) eugenol, 5% (w/v) soybean oil, 1.2% (w/v) egg phosphatidylcholine, 0.3% (w/v) poloxamer 188, and 0.03% (w/v) sodium oleate. The prepared Eug-SE was comprehensively evaluated in terms of its pharmaceutical characteristics, physicochemical stability, injection safety, antioxidant activity in vitro, and anti-epileptic effect in vivo. The mean particle size of Eug-SE was 176.1 ± 10.3 nm, the ζ-potential was -40.2 ± 1.8 mV, and the drug content was (95.3 ± 0.4) %. Moreover, the Eug-SE displayed excellent stability and improved safety compared to the eugenol solution. The Eug-SE (20 μg/mL) produced a significant neuroprotective effect against HO-induced oxidative damage in PC12 cells, which was attributed to the decrease of cellular reactive oxygen species level and mitochondrial damage. Besides, the in vivo test indicated that Eug-SE exerted an anti-epileptic effect in the PTZ treated mice. These results suggested that Eug-SE was a suitable dosage form of eugenol for injection, and displayed great therapeutic potential for neurological disease in the future.
本研究旨在开发一种丁香酚（Eug-SE）可注射亚微米乳剂，并研究其对癫痫的拮抗作用。该配方采用完全随机设计进行优化，包含 5%（w/v）丁香酚、5%（w/v）大豆油、1.2%（w/v）蛋黄卵磷脂、0.3%（w/v）泊洛沙姆 188 和 0.03%（w/v）油酸钠。综合评价了制备的 Eug-SE 的药学特性、理化稳定性、注射安全性、体外抗氧化活性和体内抗癫痫作用。Eug-SE 的平均粒径为 176.1±10.3nm，ζ-电位为-40.2±1.8mV，药物含量为（95.3±0.4）%。此外，与丁香酚溶液相比，Eug-SE 显示出更好的稳定性和更高的安全性。Eug-SE（20μg/mL）对 HO 诱导的 PC12 细胞氧化损伤具有显著的神经保护作用，这归因于细胞内活性氧水平和线粒体损伤的降低。此外，体内试验表明 Eug-SE 在 PTZ 处理的小鼠中具有抗癫痫作用。这些结果表明 Eug-SE 是一种适合注射用的丁香酚剂型，未来在神经疾病方面具有很大的治疗潜力。
