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通过皮肤输送线粒体向硫化捐赠体,AP39可以防止6 - 氧多巴胺诱导的线粒体功能障碍

Mandeep Kaur Marwah¹, Bahareh Manhoosh¹, Hala Shokr²

¹Aston Medical School, College of Health and Life Sciences, Aston University, UK.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

|September 6, 2023

概括

通过皮肤输送AP39,硫化 (H2S) 供体,显示出治疗帕金森病的前景. 这种方法有效地将AP39传递到皮肤和血脑屏障,改善神经母细胞瘤细胞中的线粒体功能.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
生物化学生物化学

背景情况:

硫化 (H2S) 是一种具有神经保护性质的信号分子.
线粒体功能障碍与帕金森病的发病有关.
开发神经保护剂的有效输送方法至关重要.

研究的目的:

评估通过皮肤输送AP39,一个线粒体向的H2S供体.
在帕金森病模型中研究AP39对抗6-氧多巴胺 (6-OH-dop) 诱导的线粒体功能障碍的能力.
为了评估AP39通过血脑屏障 (BBB) 的透性.

主要方法:

在含有不同度的烯基甘醇 (PG) 的水性高糖凝中制备AP39.
使用HPLC-UV.通过小鼠皮肤透AP39的量化.
在微血管BBB模型中评估AP39的透性.
在暴露于6-OH-dop的SHSY-5Y细胞中评估AP39对线粒体生物能和活性氧物种 (ROS) 的影响.

主要成果:

烯基醇显著增强了AP39通过小鼠皮肤的透率 (24.40%至48.59%).
AP39在BBB模型中证明了透性,随后释放了H2S.
透的AP39改善了线粒体的生物能量,并减少了6OH-dop处理的SHSY-5Y细胞中的ROS.

结论:

通过皮肤输送AP39是一种可行的方法,用于输送线粒体向的H2S供体.
这种输送方法有助于AP39穿越BBB,为治疗中枢神经系统神经退行性疾病 (如帕金森氏症) 提供了潜力.
含有10%PG的凝配方允许快速输送H2S,而无PG的凝支持持续的输送.

关键词:

硫化的供体是硫化的供体.线粒体的生物能量学神经退行性疾病的情况.持续释放的释放是一种持续释放.通过皮肤传递药物.

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