姜黄素载药明胶纳米粒通过减轻氧化应激和神经炎症治疗缺血性脑卒中。
Curcumin-Loaded Gelatin Nanoparticles Cross the Blood-Brain Barrier to Treat Ischemic Stroke by Attenuating Oxidative Stress and Neuroinflammation.
机构信息
Department of Rehabilitation Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, People's Republic of China.
Department of Psychology and Human Development, IOE, UCL's Faculty of Education and Society, University College London, London, WC1H 0AL, UK.
出版信息
Int J Nanomedicine. 2024 Nov 10;19:11633-11649. doi: 10.2147/IJN.S487628. eCollection 2024.
BACKGROUND
Ischemic stroke is a medical emergency for which effective treatment remains inadequate. Curcumin (Cur) is a natural polyphenolic compound that is regarded as a potent neuroprotective agent. Compared to synthetic pharmaceuticals, Cur possesses minimal side effects and exhibits multiple mechanisms of action, offering significant advantages in the treatment of ischemic stroke. However, drawbacks such as poor water solubility and transmembrane permeability limit the efficacy of Cur. In recent years, nano-delivery systems have attracted great interest in the field of stroke therapy as an effective method to improve drug solubility and cross the blood-brain barrier (BBB).
METHODS
In this study, a novel nanomedicine (Cur@GAR NPs) for ischemic stroke treatment was developed based on Cur-loaded gelatin nanoparticles (Cur@Gel NPs) that were then functionalized and modified with rabies virus glycoprotein (RVG29) to target brain tissue. The stability, antimicrobial properties, antioxidant properties, neuroprotective effects, neuronal cell uptake, and biocompatibility of Cur@GAR NPs were investigated in vitro. The in vivo therapeutic effect of Cur@GAR NPs on ischemic stroke was investigated in a middle cerebral artery occlusion (MCAO) rat model using the Morris water maze test and the open field test, and the potential mechanism of action was further investigated by histological analysis.
RESULTS
The resulting Cur@GAR NPs improved the solubility of Cur and exhibited good dispersion. In vitro studies have shown that Cur@GAR NPs exhibit great antimicrobial properties, antioxidant properties and intracellular reactive oxygen species (ROS) protection. Notably, RVG29 significantly enhanced the uptake of Cur@GAR NPs by SH-SY5Y cells. Furthermore, in vivo studies verified the role of Cur@GAR NPs in reducing nerve damage and supporting neurological recovery. In the MCAO rat model, Cur@GAR NPs significantly attenuated neuroinflammation, reduced neuronal apoptosis and restored behavioral functions to a great extent.
CONCLUSION
Together these findings implied that Cur@GAR NPs could provide a novel and promising approach for effective ischemic stroke treatment.
背景
缺血性中风是一种医学急症，目前仍缺乏有效的治疗方法。姜黄素（Cur）是一种天然多酚化合物，被认为是一种有效的神经保护剂。与合成药物相比，Cur 的副作用极小，且具有多种作用机制，在缺血性中风的治疗中具有显著优势。然而，Cur 水溶性差和跨膜通透性差等缺点限制了其疗效。近年来，纳米递药系统作为一种提高药物溶解度和穿越血脑屏障（BBB）的有效方法，在中风治疗领域引起了极大的兴趣。
方法
本研究基于负载姜黄素的明胶纳米粒（Cur@Gel NPs）构建了一种新型纳米药物（Cur@GAR NPs）用于治疗缺血性中风，然后用狂犬病病毒糖蛋白（RVG29）对其进行功能化和修饰，以靶向脑组织。在体外研究了 Cur@GAR NPs 的稳定性、抗菌性能、抗氧化性能、神经保护作用、神经元细胞摄取和生物相容性。通过 Morris 水迷宫试验和旷场试验在大脑中动脉闭塞（MCAO）大鼠模型中研究了 Cur@GAR NPs 对缺血性中风的体内治疗效果，并通过组织学分析进一步探讨了其潜在的作用机制。
结果
所得的 Cur@GAR NPs 提高了 Cur 的溶解度，表现出良好的分散性。体外研究表明，Cur@GAR NPs 具有良好的抗菌性能、抗氧化性能和细胞内活性氧（ROS）保护作用。值得注意的是，RVG29 显著增强了 SH-SY5Y 细胞对 Cur@GAR NPs 的摄取。此外，体内研究证实了 Cur@GAR NPs 在减轻神经损伤和支持神经功能恢复方面的作用。在 MCAO 大鼠模型中，Cur@GAR NPs 显著减轻了神经炎症，减少了神经元凋亡，并在很大程度上恢复了行为功能。
结论
综上所述，这些发现表明 Cur@GAR NPs 可为缺血性中风的有效治疗提供一种新的有前途的方法。
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