基于唾液酸的杨梅素包封阳离子纳米载体糖缀合物用于治疗阿尔茨海默病

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

作者信息

Halder Tripti, Acharya Niyati

机构信息

Department of Pharmacognosy, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, Gujarat, India.

School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, Uttarakhand, 248009, India.

出版信息

Pharm Res. 2025 Jun 9. doi: 10.1007/s11095-025-03877-5.

DOI:10.1007/s11095-025-03877-5

PMID:40490615

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.

摘要

目的

开展本研究以开发并评估用于阿尔茨海默病（AD）治疗的唾液酸接枝阳离子杨梅素（MY）制备的纳米结构脂质载体（Sia-Cat-MY-NLC）。

方法

在SH-SY5Y细胞中观察所制备纳米结构脂质载体（NLCs）的体外淀粉样β蛋白聚集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标志性物质水平。

结果

优化后的制剂中，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）。所制备的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。药代动力学研究结果表明，给予Cat-MY-NLC和Sia-Cat-MY-NLC后生物利用度分别提高了5.3倍和5.88倍。