BACKGROUND Tanshinol borneol ester (DBZ) is a hybrid of danshensu (DSS) and borneol and has anti-ischemic activity in animals. However, its low water solubility and short half-life limit its clinical application. METHODS We prepared polyethylene glycol (PEG)-modified and DBZ-loaded nanostructured lipid carriers (DBZ-PEG-NLC) and DBZ-NLC, and examined their physical characteristics, such as particle size, zeta potential, entrapment efficiency and drug loading. The in vitro stability and pharmacokinetics in rats as well as antioxidant activity of DBZ-PEG-NLC and DBZ-NLC in a C57BL/6 mouse model of ischemia/reperfusion-related brain injury were investigated. The levels of DBZ and its hydrolyzed DSS in rat plasma and brain microdialysates were determined by liquid chromatography-mass spectroscopy/mass spectroscopy analysis. RESULTS We found that the mean particle size and entrapment efficacy of DBZ-PEG-NLC were similar to that of DBZ-NLC. The DBZ-PEG-NLC, like DBZ-NLC, released DBZ in a biphasic manner with initially burst release and then prolonged slow release in vitro. Intravenous injection of DBZ-PEG-NLC resulted in significantly higher levels and longer retention periods of DBZ and DSS in plasma and the brains than DBZ-NLC and DBZ in rats. Finally, treatment with DBZ-PEG-NLC achieved a better antioxidant activity than DBZ or DBZ-NLC in mouse model of ischemia/reperfusion by reducing the levels of brain malondialdehyde, but increasing the levels of brain superoxide dismutase and glutathione. CONCLUSION DBZ-PEG-NLC is a preferable option to deliver DBZ for sustainable release of DSS and borneol in vivo, and may serve as a promising drug for effective therapy of ischemic cardiovascular and cerebrovascular diseases.

中文翻译：

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纳米结构脂质载体上的丹参醇冰片酯具有更长的脑和全身效应保留时间和更好的体内抗氧化活性。

背景技术丹参醇冰片酯(DBZ)是丹参素(DSS)和冰片的混合物，在动物体内具有抗缺血活性。但其水溶性低、半衰期短限制了其临床应用。方法我们制备了聚乙二醇（PEG）修饰和负载DBZ的纳米结构脂质载体（DBZ-PEG-NLC）和DBZ-NLC，并检查了它们的物理特性，如粒径、zeta电位、包封率和载药量。研究了大鼠体外稳定性和药代动力学以及 DBZ-PEG-NLC 和 DBZ-NLC 在 C57BL/6 小鼠缺血/再灌注相关脑损伤模型中的抗氧化活性。通过液相色谱-质谱/质谱分析测定大鼠血浆和脑微透析液中 DBZ 及其水解 DSS 的水平。结果我们发现DBZ-PEG-NLC的平均粒径和包封率与DBZ-NLC相似。DBZ-PEG-NLC 与 DBZ-NLC 一样，以双相方式释放 DBZ，最初是突释，然后在体外延长缓慢释放。与 DBZ-NLC 和 DBZ 在大鼠中相比，DBZ-PEG-NLC 的静脉注射导致血浆和脑中 DBZ 和 DSS 的水平显着升高且保留期更长。最后，通过降低脑丙二醛水平，但增加脑超氧化物歧化酶和谷胱甘肽水平，DBZ-PEG-NLC 治疗在缺血/再灌注小鼠模型中实现了比 DBZ 或 DBZ-NLC 更好的抗氧化活性。结论 DBZ-PEG-NLC 是提供 DBZ 以在体内可持续释放 DSS 和冰片的优选选择，