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

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech 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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Abstract

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.

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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

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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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.