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使用[具体模型1]和[具体模型2]制备并评估用于抗癌和抗抑郁作用的薯蓣皂苷元包封硬脂酸固体脂质纳米粒

Fabrication and Assessment of Diosgenin Encapsulated Stearic Acid Solid Lipid Nanoparticles for Its Anticancer and Antidepressant Effects Using and Models.

作者信息

Khan Hina, Nazir Sadia, Farooq Rai Khalid, Khan Ishaq N, Javed Aneela

机构信息

Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

Department of Neuroscience Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

出版信息

Front Neurosci. 2022 Feb 10;15:806713. doi: 10.3389/fnins.2021.806713. eCollection 2021.

Abstract

Inflammatory cascade plays a pivotal role in the onset and progression of major depressive disorder (MDD) and glioblastoma multiforme (GBM). Therefore, questing natural compounds with anti-inflammatory activity such as diosgenin can act as a double-edged sword targeting cancer and cancer-induced inflammation simultaneously. The blood-brain barrier limits the therapeutic efficiency of the drugs against intracranial pathologies including depression and brain cancers. Encapsulating a drug molecule in lipid nanoparticles can overcome this obstacle. The current study has thus investigated the anticancer and antidepressant effect of Tween 80 (P80) coated stearic acid solid lipid nanoparticles (SLNPs) encapsulating the diosgenin. Physio-chemical characterizations of SLNPs were performed to assess their stability, monodispersity, and entrapment efficiency. cytotoxic analysis of naked and drug encapsulated SLNPs on U-87 cell line indicated diosgenin IC value to be 194.4 μM, while diosgenin encapsulation in nanoparticles slightly decreases the toxicity. Antidepressant effects of encapsulated and non-encapsulated diosgenin were comprehensively evaluated in the concanavalin-A-induced sickness behavior mouse model. Behavior test results indicate that diosgenin and diosgenin encapsulated nanoparticles significantly alleviated anxiety-like and depressive behavior. Diosgenin incorporated SLNPs also improved grooming behavior and social interaction as well as showed normal levels of neutrophils and leukocytes with no toxicity indication. In conclusion, diosgenin and diosgenin encapsulated solid lipid nanoparticles proved successful in decreasing cancer cell proliferation and improving sickness behavioral phenotype and thus merit further exploration.

摘要

炎症级联反应在重度抑郁症(MDD)和多形性胶质母细胞瘤(GBM)的发病和进展中起关键作用。因此,寻找具有抗炎活性的天然化合物,如薯蓣皂苷元,可同时作为针对癌症和癌症诱导炎症的双刃剑。血脑屏障限制了药物对包括抑郁症和脑癌在内的颅内疾病的治疗效果。将药物分子包裹在脂质纳米颗粒中可以克服这一障碍。因此,本研究调查了包裹薯蓣皂苷元的吐温80(P80)包被硬脂酸固体脂质纳米颗粒(SLNPs)的抗癌和抗抑郁作用。对SLNPs进行了物理化学表征,以评估其稳定性、单分散性和包封效率。对未包载和包载药物的SLNPs对U-87细胞系的细胞毒性分析表明,薯蓣皂苷元的IC值为194.4 μM,而纳米颗粒中薯蓣皂苷元的包封略微降低了毒性。在伴刀豆球蛋白A诱导的疾病行为小鼠模型中全面评估了包载和未包载薯蓣皂苷元的抗抑郁作用。行为测试结果表明,薯蓣皂苷元和包载薯蓣皂苷元的纳米颗粒显著减轻了焦虑样和抑郁行为。掺入薯蓣皂苷元的SLNPs还改善了梳理行为和社交互动,并且显示中性粒细胞和白细胞水平正常,没有毒性迹象。总之,薯蓣皂苷元和包载薯蓣皂苷元的固体脂质纳米颗粒在降低癌细胞增殖和改善疾病行为表型方面取得了成功,因此值得进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2086/8866708/c123e22a624c/fnins-15-806713-g001.jpg

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