水飞蓟宾包裹纳米液体晶体在体内模型中抗 Aβ1-42 神经毒性活性的制备与表征

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-07-01 DOI:10.1208/s12249-024-02859-x

Ajit Singh, Debarati Rakshit, Ankit Kumar, Awanish Mishra, Rahul Shukla

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摘要

研究人员制备了水飞蓟宾（SIL）包裹纳米液晶（SIL-NLCs）颗粒，以研究其对 Balb/c 小鼠模型中淀粉样 beta（Aβ1-42）神经毒性的保护作用。这些 NLCs 是通过热乳化和探针超声技术制备的。对脑室内注射 Aβ1-42（ICV）的 Balb/c 小鼠进行了药效学研究。优化后的粒度、ZETA电位和载药量分别为 153 ± 2.5 nm、-21 mV 和 8.2%。小角 X 射线（SAXS）和电子显微镜显示了 SIL-NLCs 的结晶形状。利用硫黄素 T（ThT）荧光光谱和圆二色性（CD）技术了解了 SIL-NLCs 对 Aβ1-4 的单体抑制作用。在神经行为学研究中，SIL-NLCs 在 T 型迷宫和新物体识别试验（NORT）中对 Aβ1-42 引起的记忆损伤有增强的缓解作用。脑样本的生化和组织病理学评估显示，Aβ1-42 聚集体、乙酰胆碱酯酶（ACHE）和活性氧（ROS）的水平有所下降。与游离 SIL 和多诺哌齐（DPZ）相比，经 SIL-NLCs 处理的动物组对 Aβ1-42 的毒性具有更高的保护作用。因此，SIL-NLCs 在阿尔茨海默病等神经退行性疾病中具有广阔的应用前景。

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Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aβ1-42 Neurotoxicity in In-Vivo Model

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aβ_1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aβ_1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aβ_1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aβ_1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aβ_1–42 aggregate_, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aβ_1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer’s disease.