Enhanced Neuroprotective Effects of Resveratrol Delivered by Nanoparticles on Hydrogen Peroxide-Induced Oxidative Stress in Rat Cortical Cell Culture
Enhanced Neuroprotective Effects of Resveratrol Delivered by Nanoparticles on Hydrogen Peroxide-Induced Oxidative Stress in Rat Cortical Cell Culture
复制标题
纳米颗粒提供的白藜芦醇对大鼠皮层细胞培养物中过氧化氢诱导的氧化应激的增强神经保护作用
DOI：
10.1021/mp400056c
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发表时间：
2013-05-01
影响因子：
4.9
通讯作者：
Li, Xiaolin
中科院分区：
文献类型：
--
作者：
Lu, Xiaowei;Xu, Huae;Li, Xiaolin
白藜芦醇（Resveratrol，RES）是一种潜在的抗氧化剂，可通过减轻氧化应激和细胞凋亡来治疗缺血/再灌注损伤。然而，RES的不溶性和半衰期短限制了其应用。最新的证据提出了开发具有改善的溶解性、稳定性和亲脂性药物的细胞毒性的基于纳米颗粒的递送系统的可能性。在这里，我们首先报道了一种简单的方法来生产基于聚（N-乙烯基吡咯烷酮）-b-聚（ε-己内酯）聚合物的RES-负载的纳米粒子（RES-NPs），并进一步评估RES-NPs对过氧化氢诱导的氧化应激和大鼠皮层细胞培养中的凋亡的保护作用。通过体外释放实验对纳米粒的控释模式进行了表征。细胞毒性试验证明了这些纳米颗粒与神经元的细胞相容性。通过负载香豆素-6的纳米颗粒显示，神经元对纳米颗粒的摄取被认为是通过内吞作用，这可以在较低浓度下导致较高的摄取效率。因此，提出了这样的假设，即RES-NPs可以表现出增强的神经保护作用，特别是与较低浓度的等效剂量的游离RES相比。LDH释放的减少、ROS和MDA的清除以及凋亡信号（Bax/Bcl-2比值、caspase-3的活化）的减弱进一步支持了该作用。RES-NPs可能是一种潜在的治疗方法，需要对缺血/再灌注相关疾病（包括中风）进行深入研究。
Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(epsilon-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower, concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke.