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负载金诺芬的聚乳酸-羟基乙酸共聚物纳米颗粒对铝诱导的阿尔茨海默病的神经保护作用

Auranofin-loaded PLGA Nanoparticles for Neuroprotection against Aluminium-induced Alzheimer's Disease.

作者信息

Kushwaha Shiv Kumar, Ashawat Mahendra Singh, Arora Rimpi, Baldi Ashish

机构信息

Pharma Innovation Lab, Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, 151001, India.

Department of Pharmaceutics, Laureate Institute of Pharmacy, Kathog, Distt. Kangra, H.P. 176031, India.

出版信息

Curr Pharm Des. 2025 Jan 17. doi: 10.2174/0113816128336703241202182209.

Abstract

AIM

The aim of the current study was to explore nano-formulation for effective neuroprotection by auranofin.

BACKGROUND

Currently, the treatment options for various CNS disorders, particularly neurodegenerative disorders, are greatly constrained. A significant obstacle in this pursuit is the blood-brain barrier, a shielding covering that hinders the route of numerous biochemical treatments into the brain. To overcome this problem, nanoformulation- based approaches are gaining interest, increasing the compound's BBB penetrability.

OBJECTIVE

The objective of this study was to evaluate whether nanoparticles fabricated from poly(lactic-co-glycolic acid) encapsulated with auranofin could oppose aluminium chloride-induced Alzheimer's disease.

METHOD

Auranofin-encapsulated PLGA nanoparticles were prepared, and their particle size, Entrapment Efficiency (EE), distribution of particles, morphological surface charge, and structural characteristics were characterized. During the in vivo study, rats were orally administered AlCl3 at 100 mg/kg for 21 days. Meanwhile, auranofin and auranofin nanoparticles were orally administered at doses of 5 and 10 mg/kg and 2.5 and 5 mg/kg, respectively, within 2 weeks. After the course therapy, the rats were decapitated, and the hippocampus was collected for the estimated biochemical and neuroinflammatory markers.

RESULTS

The auranofin nanoparticles were characterized, revealing % entrapment efficiency (98%) and % loading dose (76%). The nanoparticles exhibited a morphological surface charge of 27.5 ± 5.10 mV, a polydispersity index of 0.438 ± 0.12, and a mean particle size of 101.5 ± 10.3 nm. In the in vivo study, administering a gold compound (auranofin) and formulation (auranofin nanoparticles) resulted in a significant improvement in cognitive deficits, changes in biochemical parameters, and markers of neuroinflammation triggered with aluminium chloride.

CONCLUSION

The results have suggested that auranofin nanoparticles demonstrate abilities to protect neurons compared to auranofin alone. The noticed therapeutic benefits of the auranofin-encapsulated PLGA nanoparticles can be attributed to modulation in particle size with antioxidative and anti-inflammatory impacts of auranofin. Consequently, the outcome of the research has revealed that gold compound nanoparticles hold the potential to be a promising option for altering the therapeutic course of Alzheimer's disease.

摘要

目的

本研究旨在探索金诺芬的纳米制剂以实现有效的神经保护作用。

背景

目前,各种中枢神经系统疾病,特别是神经退行性疾病的治疗选择受到极大限制。这一研究过程中的一个重大障碍是血脑屏障,它是一种屏蔽层,阻碍了许多生化治疗药物进入大脑的途径。为克服这一问题,基于纳米制剂的方法正受到关注,可提高化合物的血脑屏障穿透性。

目的

本研究的目的是评估由包裹金诺芬的聚乳酸-羟基乙酸共聚物制成的纳米颗粒是否能对抗氯化铝诱导的阿尔茨海默病。

方法

制备了包裹金诺芬的聚乳酸-羟基乙酸共聚物纳米颗粒,并对其粒径、包封率(EE)、颗粒分布、形态表面电荷和结构特征进行了表征。在体内研究中,大鼠以100mg/kg的剂量口服氯化铝,持续21天。同时,在2周内分别以5mg/kg和10mg/kg以及2.5mg/kg和5mg/kg的剂量口服金诺芬和金诺芬纳米颗粒。疗程结束后,将大鼠断头,收集海马体以评估生化和神经炎症标志物。

结果

对金诺芬纳米颗粒进行了表征,其包封率为98%,载药量为76%。纳米颗粒的形态表面电荷为27.5±5.10mV,多分散指数为0.438±0.12,平均粒径为101.5±10.3nm。在体内研究中,给予金化合物(金诺芬)和制剂(金诺芬纳米颗粒)可显著改善由氯化铝引发的认知缺陷、生化参数变化和神经炎症标志物。

结论

结果表明,与单独的金诺芬相比,金诺芬纳米颗粒具有保护神经元的能力。包裹金诺芬的聚乳酸-羟基乙酸共聚物纳米颗粒所观察到的治疗益处可归因于粒径的调节以及金诺芬的抗氧化和抗炎作用。因此,研究结果表明金化合物纳米颗粒有可能成为改变阿尔茨海默病治疗进程的有前景的选择。

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