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负载吲哚 - 3 - 甲醇的聚乳酸 - 乙醇酸共聚物纳米颗粒对谷氨酸诱导的神经毒性的保护作用

Protective Effects of Indole-3-Carbinol-Loaded Poly(lactic-co-glycolic acid) Nanoparticles Against Glutamate-Induced Neurotoxicity.

作者信息

Jeong Ji Heun, Kim Jwa-Jin, Bak Dong Ho, Yu Kwang Sik, Lee Je Hun, Lee Nam Seob, Jeong Young Gil, Kim Do Kyung, Kim Dong-Kwan, Han Seung-Yun

出版信息

J Nanosci Nanotechnol. 2015 Oct;15(10):7922-8. doi: 10.1166/jnn.2015.11219.

Abstract

Indole-3-carbinol (I3C) has anti-oxidant and anti-inflammatory properties. Nonetheless, the potential of I3C to treat neurodegenerative diseases remains unclear because of its poor ability to penetrate the blood-brain barrier (BBB). Because polymer-based drug delivery systems stabilized by surfactants have been intensively utilized as a strategy to cross the blood-brain barrier, we prepared I3C-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that were stabilized by Tween 80 (T80) (I3C-PLGA-T80-NPs) and examined their neuroprotective potential in vitro. We prepared I3C-PLGA-T80-NPs with an oil-in-water (o/w) emulsion solvent evaporation technique and confirmed their successful synthesis with both transmission electron microscopy and Fourier transform-infrared spectroscopy. I3C-PLGA-T80-NPs were then used to treat PC12 neuronal cells injured by glutamate excitotoxicity (GE) and examined the resulting survival rates compared with PC12 cells treated with I3C only. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed higher survival rates in I3C-PLGA-T80-NPs-treated cells after GE injury compared with those treated with I3C only. Furthermore, I3C-PLGA-T80-NPs decreased the levels of reactive oxygen species (ROS) and apoptosis-related enzymes (Caspase-3 and -8) in GE-damaged neuronal cells. Taken together, I3C-PLGA-T80-NPs might possess neuroprotective effects against GE through ROS scavenging and subsequent apoptosis blockage.

摘要

吲哚 - 3 - 甲醇(I3C)具有抗氧化和抗炎特性。然而,由于其穿透血脑屏障(BBB)的能力较差,I3C治疗神经退行性疾病的潜力仍不明确。由于由表面活性剂稳定的基于聚合物的药物递送系统已被广泛用作穿越血脑屏障的策略,我们制备了由吐温80(T80)稳定的载有I3C的聚(D,L - 乳酸 - 乙醇酸共聚物)(PLGA)纳米颗粒(NPs)(I3C - PLGA - T80 - NPs),并在体外研究了它们的神经保护潜力。我们采用水包油(o/w)乳液溶剂蒸发技术制备了I3C - PLGA - T80 - NPs,并通过透射电子显微镜和傅里叶变换红外光谱证实了它们的成功合成。然后,用I3C - PLGA - T80 - NPs处理受谷氨酸兴奋性毒性(GE)损伤的PC12神经元细胞,并与仅用I3C处理的PC12细胞相比,检测由此产生的存活率。3 - [4,5 - 二甲基噻唑 - 2 - 基] - 2,5 - 二苯基四氮唑溴盐(MTT)测定显示,与仅用I3C处理的细胞相比,GE损伤后用I3C - PLGA - T80 - NPs处理的细胞存活率更高。此外,I3C - PLGA - T80 - NPs降低了GE损伤的神经元细胞中活性氧(ROS)和凋亡相关酶(半胱天冬酶 - 3和 - 8)的水平。综上所述,I3C - PLGA - T80 - NPs可能通过清除ROS和随后阻断凋亡而对GE具有神经保护作用。

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