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Sonodynamic therapy in atherosclerosis by curcumin nanosuspensions: Preparation design, efficacy evaluation, and mechanisms analysis.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-12-11 , DOI: 10.1016/j.ejpb.2019.12.005 Lei Jiang 1 , Jiahe Wang 1 , Jiaqi Jiang 1 , Changmei Zhang 1 , Man Zhao 1 , Zhong Chen 1 , Na Wang 1 , Dandan Hu 1 , Xiaoying Liu 1 , Haisheng Peng 1 , Mingming Lian 1
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-12-11 , DOI: 10.1016/j.ejpb.2019.12.005 Lei Jiang 1 , Jiahe Wang 1 , Jiaqi Jiang 1 , Changmei Zhang 1 , Man Zhao 1 , Zhong Chen 1 , Na Wang 1 , Dandan Hu 1 , Xiaoying Liu 1 , Haisheng Peng 1 , Mingming Lian 1
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Previous studies have shown that curcumin (Cur) induced by ultrasound has protective effects on atherosclerosis even if low bioavailability of the Cur. The enhancement of bioavailability of the Cur further improved the curative effect of sonodynamic therapy (SDT) on atherosclerosis through nanotechnology. Nanosuspensions as a good drug delivery system had obvious advantages in increasing the solubility and improving the effectiveness of insoluble drugs. The aim of this study was to develop curcumin nanosuspensions (Cur-ns) which used polyvinylpyrrolidone (PVPK30) and sodium dodecyl sulfate (SDS) as stabilizers to improve poor water solubility and bioavailability of the Cur. And then the therapeutic effects of Cur-ns-SDT on atherosclerotic plaques and its possible mechanisms would be investigated and elucidated. Cur-ns with a small particle size has been successfully prepared and the data have confirmed that Cur-ns could be more easily engulfed into RAW264.7 cells than free Cur and accumulated more under the stimulation of the ultrasound. Reactive oxygen species (ROS) inside RAW264.7 cells after SDT led to the decrease of mitochondrial membrane potential (MMP) and the higher expression of cleaved caspase-9/3. The results of in vivo experiments showed that Cur-ns-SDT reduced the level of total cholesterol (TC) and low density lipoprotein (LDL) and promoted the transformation from M1 to M2 macrophages, relieved atherosclerosis syndrome. Therefore, Cur-ns-SDT was a potential treatment of anti-atherosclerosis by enhancing macrophages apoptosis through mitochondrial pathway and inhibiting the progression of plaques by interfering with macrophages polarization.
中文翻译：
姜黄素纳米悬浮液在动脉粥样硬化中的声动力疗法：制备设计，疗效评估和机理分析。
先前的研究表明，即使Cur的生物利用度较低，超声诱导的姜黄素（Cur）对动脉粥样硬化也具有保护作用。Cur的生物利用度的提高通过纳米技术进一步改善了声动力疗法（SDT）对动脉粥样硬化的疗效。纳米混悬剂作为良好的药物递送系统在增加溶解度和提高不溶性药物的有效性方面具有明显的优势。这项研究的目的是开发姜黄素纳米悬浮液（Cur-ns），该悬浮液使用聚乙烯吡咯烷酮（PVPK30）和十二烷基硫酸钠（SDS）作为稳定剂，以改善Cur的不良水溶性和生物利用度。然后研究并阐明Cur-ns-SDT对动脉粥样硬化斑块的治疗作用及其可能的机制。已经成功制备了具有小粒径的Cur-ns，并且数据已经证实，与游离Cur相比，Cur-ns更容易被RAW264.7细胞吞噬，并且在超声的刺激下会积累更多。SDT后RAW264.7细胞内的活性氧（ROS）导致线粒体膜电位（MMP）的降低和裂解的caspase-9 / 3的高表达。体内实验结果表明，Cur-ns-SDT降低了总胆固醇（TC）和低密度脂蛋白（LDL）的水平，并促进了从M1到M2巨噬细胞的转化，从而缓解了动脉粥样硬化综合征。因此，Cur-ns-SDT可通过线粒体途径增强巨噬细胞凋亡，并通过干扰巨噬细胞极化抑制噬菌斑的进展，从而成为抗动脉粥样硬化的潜在疗法。
更新日期：2019-12-11
中文翻译：
姜黄素纳米悬浮液在动脉粥样硬化中的声动力疗法：制备设计，疗效评估和机理分析。
先前的研究表明，即使Cur的生物利用度较低，超声诱导的姜黄素（Cur）对动脉粥样硬化也具有保护作用。Cur的生物利用度的提高通过纳米技术进一步改善了声动力疗法（SDT）对动脉粥样硬化的疗效。纳米混悬剂作为良好的药物递送系统在增加溶解度和提高不溶性药物的有效性方面具有明显的优势。这项研究的目的是开发姜黄素纳米悬浮液（Cur-ns），该悬浮液使用聚乙烯吡咯烷酮（PVPK30）和十二烷基硫酸钠（SDS）作为稳定剂，以改善Cur的不良水溶性和生物利用度。然后研究并阐明Cur-ns-SDT对动脉粥样硬化斑块的治疗作用及其可能的机制。已经成功制备了具有小粒径的Cur-ns，并且数据已经证实，与游离Cur相比，Cur-ns更容易被RAW264.7细胞吞噬，并且在超声的刺激下会积累更多。SDT后RAW264.7细胞内的活性氧（ROS）导致线粒体膜电位（MMP）的降低和裂解的caspase-9 / 3的高表达。体内实验结果表明，Cur-ns-SDT降低了总胆固醇（TC）和低密度脂蛋白（LDL）的水平，并促进了从M1到M2巨噬细胞的转化，从而缓解了动脉粥样硬化综合征。因此，Cur-ns-SDT可通过线粒体途径增强巨噬细胞凋亡，并通过干扰巨噬细胞极化抑制噬菌斑的进展，从而成为抗动脉粥样硬化的潜在疗法。
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