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水飞蓟宾纳米液晶包合物提高了抗β淀粉样蛋白诱导细胞毒性的活性。

Silymarin encapsulated nanoliquid crystals for improved activity against beta amyloid induced cytotoxicity.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER-R)-Raebareli, Lucknow, Uttar Pradesh 226002, India.

Institute of Nano Science and Technology (INST), Phase X, Sector 64, Mohali, Punjab 12 160062, India.

出版信息

Int J Biol Macromol. 2020 Apr 15;149:1198-1206. doi: 10.1016/j.ijbiomac.2020.02.041. Epub 2020 Feb 7.

Abstract

Silymarin (SLY) a natural Aβ aggregation inhibitor, antioxidant and act as neuroprotectant. In the present study, we have prepared nano liquid crystals (NLCs) of negatively charged glycerylmonooleate (GMO) loaded with SLY for enhancing activity against Aβ induced toxicity. SLY-NLCs are characterized for physicochemical parameters such as particle size, zeta potential, and drug-loading. The average particle size, zeta potential and % DL were found ≤200 nm, -22 mV, and 8.73% respectively. The amorphous form and entrapment of SLY in NLC were confirmed using DSC and FTIR analysis. The cubosomal SLY-NLCs shape was characterized by SEM and TEM. The cumulative drug release of SLY was ~76% at pH 7.4 (cerebrospinal fluid) from lyophilized SLY-NLC in 48 h. In order to understand the Aβ aggregation inhibition due to SLY-NLC ThT (Thioflavin T) kinetic binding assay was also performed. The cell viability assessment of SLY-NLC was performed on SHSY5Y cell line that showed the highest viability in comparison to free SLY treated groups. ROS and apoptosis activity study SLY-NLCs reduced the Aβ induced free radical with cell death. Cellular uptake study proved enhanced intracellular internalization of FITC tagged NLCs in 24 h. SLY-NLCs can offer great prospects in the field of drug delivery for neuroprotection.

摘要

水飞蓟宾(SLY)是一种天然的 Aβ 聚集抑制剂,具有抗氧化和神经保护作用。在本研究中,我们制备了带负电荷的甘油脂(GMO)载有水飞蓟宾的纳米液晶(NLC),以增强其对 Aβ 诱导毒性的活性。SLY-NLC 的理化参数如粒径、Zeta 电位和载药量进行了表征。平均粒径、Zeta 电位和载药量分别为≤200nm、-22mV 和 8.73%。DSC 和 FTIR 分析证实了 SLY 的无定形形式和在 NLC 中的包埋。SEM 和 TEM 对立方体型 SLY-NLC 的形状进行了表征。在 pH7.4(脑脊液)下,冻干的 SLY-NLC 在 48 小时内的累积药物释放率约为 76%。为了了解 SLY-NLC 对 Aβ 聚集的抑制作用,还进行了 ThT(硫黄素 T)动力学结合测定。在 SHSY5Y 细胞系上进行了 SLY-NLC 的细胞活力评估,与游离 SLY 处理组相比,其细胞活力最高。ROS 和凋亡活性研究表明,SLY-NLC 降低了 Aβ 诱导的自由基并减少了细胞死亡。细胞摄取研究证明,在 24 小时内,FITC 标记的 NLCs 增强了细胞内内化。SLY-NLC 在神经保护药物递送领域具有广阔的前景。

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