负载绿茶提取物的壳聚糖修饰PLGA纳米颗粒具有抑制β淀粉样肽聚集和氧化应激的作用

IF 5.2 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Liquids Pub Date : 2025-10-02 DOI:10.1016/j.molliq.2025.128650

Stéphanie Andrade , Maria J. Ramalho , Joana A. Loureiro , Maria C. Pereira

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引用次数: 0

摘要

阿尔茨海默病（AD）与大脑中β淀粉样蛋白（Aβ）斑块沉积有关，通过炎症和氧化应激导致神经毒性。由于绿茶具有抗淀粉样变性、抗炎和抗氧化的特性，它在治疗阿尔茨海默病方面显示出了希望。然而，绿茶提取物（GTE）的治疗效果受到其主要成分生物利用度低和通过血脑屏障能力差的限制。纳米颗粒（NPs）设计用于鼻子到大脑的传递，通过增强GTE到大脑的靶向传递提供了一种解决方案。本研究制备了壳聚糖（Ch）修饰的聚乳酸-羟基乙酸（PLGA） NPs，用于GTE脑递送。gte负载的ch修饰的PLGA NPs具有适合脑递送的物理化学特性，包括平均直径为274±15 nm的球形形貌和均匀的尺寸分布。NPs包封效率为41±8%，zeta电位为9±4 mV。它们在储存条件下保持了长达3个月的胶体稳定性，并且释放动力学显示出控制和持续释放的特征，在6天内释放了32±10%的GTE。此外，NPs通过与粘蛋白的相互作用证实了其粘接特性。重要的是，NPs通过有效阻止Aβ聚集显示出强大的抗淀粉样蛋白生成活性，其抗氧化活性为88±4%。该研究为黏附PLGA NPs用于GTE递送的潜力提供了有价值的见解，代表了通过靶向关键疾病机制来管理AD的治疗策略的重大进展。

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Mucoadhesive chitosan-modified PLGA nanoparticles loaded with green tea extract inhibit amyloid β peptide aggregation and oxidative stress

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Mucoadhesive chitosan-modified PLGA nanoparticles loaded with green tea extract inhibit amyloid β peptide aggregation and oxidative stress

Alzheimer's disease (AD) is associated with amyloid β (Aβ) plaque deposition in the brain, which leads to neurotoxicity through inflammation and oxidative stress. Green tea has shown promise in treating AD due to its anti-amyloidogenic, anti-inflammatory, and antioxidant properties. However, the therapeutic efficacy of green tea extract (GTE) is limited by the low bioavailability of its main constituents and their poor ability to cross the blood-brain barrier. Nanoparticles (NPs) designed for nose-to-brain delivery offer a solution by enhancing the targeted delivery of GTE to the brain. In this study, poly(lactic-co-glycolic) acid (PLGA) NPs modified with chitosan (Ch) were developed for brain delivery of GTE. GTE-loaded Ch-modified PLGA NPs exhibited suitable physicochemical characteristics for brain delivery, including a spherical morphology with an average diameter of 274 ± 15 nm and a uniform size distribution. The NPs showed an encapsulation efficiency of 41 ± 8 % and a positive zeta potential of 9 ± 4 mV. They retained their colloidal stability in storage conditions for up to 3 months, and the release kinetics demonstrated a controlled and sustained release profile, with 32 ± 10 % of GTE released over 6 days. Additionally, the NPs' mucoadhesive properties were confirmed through their interactions with mucin. Importantly, the NPs exhibited strong anti-amyloidogenic activity by effectively preventing Aβ aggregation, along with an antioxidant activity of 88 ± 4 %. This study provides valuable insights into the potential of mucoadhesive PLGA NPs for GTE delivery, representing a significant advancement in therapeutic strategies for managing AD by targeting critical disease mechanisms.

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来源期刊

Journal of Molecular Liquids 化学-物理：原子、分子和化学物理

CiteScore

10.30

自引率

16.70%

发文量

2597

审稿时长

78 days

期刊介绍： The journal includes papers in the following areas: – Simple organic liquids and mixtures – Ionic liquids – Surfactant solutions (including micelles and vesicles) and liquid interfaces – Colloidal solutions and nanoparticles – Thermotropic and lyotropic liquid crystals – Ferrofluids – Water, aqueous solutions and other hydrogen-bonded liquids – Lubricants, polymer solutions and melts – Molten metals and salts – Phase transitions and critical phenomena in liquids and confined fluids – Self assembly in complex liquids.– Biomolecules in solution The emphasis is on the molecular (or microscopic) understanding of particular liquids or liquid systems, especially concerning structure, dynamics and intermolecular forces. The experimental techniques used may include: – Conventional spectroscopy (mid-IR and far-IR, Raman, NMR, etc.) – Non-linear optics and time resolved spectroscopy (psec, fsec, asec, ISRS, etc.) – Light scattering (Rayleigh, Brillouin, PCS, etc.) – Dielectric relaxation – X-ray and neutron scattering and diffraction. Experimental studies, computer simulations (MD or MC) and analytical theory will be considered for publication; papers just reporting experimental results that do not contribute to the understanding of the fundamentals of molecular and ionic liquids will not be accepted. Only papers of a non-routine nature and advancing the field will be considered for publication.