Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-06-09 DOI:10.1007/s11095-025-03877-5

Tripti Halder, Niyati Acharya

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引用次数: 0

Abstract

Purpose: The current study was conducted to develop and evaluate sialic acid grafted cationic myricetin (MY) fabricated nanostructured lipid carrier (Sia-Cat-MY-NLC) for Alzheimer's disease (AD) management.

Methods: In-vitro amyloid beta aggregation inhibition and mitochondrial membrane potential of prepared NLCs were observed in SH-SY5Y cells. The transendothelial electrical resistance was measured through hCMEC/D3 cells. Pharmacokinetic and pharmacodynamic studies were conducted to evaluate neuropharmacokinetic parameters and levels of AD hallmarks in AD rats.

Results: The optimized formulations showed particle sizes (142.26 ± 24.16 nm and 236.3 ± 15.26 nm), zeta potentials (36.5 ± 2.43 mv and -2.4 ± 1.30 mv) respectively for Cat-MY-NLC and Sia-Cat-MY-NLC. Prepared NLCs treatments revealed significant neuroprotective effects in SH-SY5Y cells followed by the ability to cross the in-vitro BBB model. Results of pharmacokinetic studies showed 5.3 and 5.88 folds enhanced bioavailability with Cat-MY-NLC and Sia-Cat-MY-NLC administration respectively.

Conclusions: The results of enzymatic analysis showed a significant (p < 0.05) restoration of AD hallmark levels in the brain after Sia-Cat-MY-NLC treatment than Cat-MY-NLC.

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杨梅素包封的阳离子纳米载体唾液酸糖缀合治疗阿尔茨海默病。

目的：本研究旨在开发和评估唾液酸移植阳离子杨梅素（MY）制备的纳米结构脂质载体（Sia-Cat-MY-NLC）对阿尔茨海默病（AD）的治疗作用。方法：在SH-SY5Y细胞中观察制备的NLCs体外对β淀粉样蛋白聚集的抑制作用和线粒体膜电位。通过hCMEC/D3细胞测量跨内皮电阻。进行了药代动力学和药效学研究，以评估AD大鼠的神经药代动力学参数和AD标志物水平。结果：Cat-MY-NLC和Sia-Cat-MY-NLC的粒径分别为142.26±24.16 nm和236.3±15.26 nm， zeta电位分别为36.5±2.43 mv和-2.4±1.30 mv。制备的NLCs处理在SH-SY5Y细胞中显示出显著的神经保护作用，随后能够穿过体外血脑屏障模型。药动学研究结果显示，Cat-MY-NLC和Sia-Cat-MY-NLC的生物利用度分别提高了5.3倍和5.88倍。结论：酶分析结果显示了显著的(p

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.