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通过反相乳液法合成含希夫碱的牛血清白蛋白-阿拉伯胶醛混合纳米凝胶及其作为抗癌药物载体的研究

Synthesis and characterization of Schiff base containing bovine serum albumin-gum arabic aldehyde hybrid nanogels via inverse miniemulsion for delivery of anticancer drug.

机构信息

Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, PO Box: 14155-114, Iran.

Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, PO Box: 14155-114, Iran.

出版信息

Int J Biol Macromol. 2021 Feb 15;170:222-231. doi: 10.1016/j.ijbiomac.2020.12.150. Epub 2020 Dec 29.

DOI:10.1016/j.ijbiomac.2020.12.150
PMID:33359811
Abstract

The periodate modified gum arabic was used as a natural-based, non-toxic cross-linker to synthesize hybrid bovine serum albumin-gum arabic aldehyde (BSA-GAA) nanogels by Schiff base reaction through the inverse miniemulsion method for the first time. The synthesis process was performed in the absence of toxic organic solvents using fractionated coconut oil as the continuous phase. The particle size of the nanogels was managed by tweaking the concentration of the surfactants (Span 80/Tween 80) and the total volume of the aqueous phase. Based on the bicinchoninic acid method, the cross-linking efficiency of BSA and GAA was estimated at 98%. 5-fluorouracil (5-FU) was selected as the sample drug. The 5-FU-loaded hybrid nanogels showed a spherical morphology with an average diameter of 231.33 ±12.74 nm and a zeta potential of -31.6 mV. The encapsulation and loading efficiency of the nanogels were calculated at 42 ± 4.52% and 2.37 ± 0.59%, respectively. The properties of the hybrid nanogels were analyzed by dynamic light scattering (DLS), Fourier transform infrared microscopy (FTIR) analysis, field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). The pH sensitivity of the hybrid nanogels was confirmed by the in vitro release profiles of 5-FU in different buffers. Hemolysis assay revealed the in vitro hemocompatibility of the hybrid nanogels which inhibited the growth of MCF-7 cells with an IC50 value of 16.21 μM. The present study suggested that these biobased hybrid nanogels could have a great potential in drug delivery and other biomedical applications.

摘要

过碘酸修饰的阿拉伯胶被用作一种天然的、无毒的交联剂,通过席夫碱反应,首次通过反相乳液法合成了混合牛血清白蛋白-阿拉伯胶醛(BSA-GAA)纳米凝胶。该合成过程在没有有毒有机溶剂的情况下进行,使用分馏椰子油作为连续相。纳米凝胶的粒径通过调整表面活性剂(Span 80/Tween 80)的浓度和水相的总体积来控制。根据双缩脲法,BSA 和 GAA 的交联效率估计为 98%。选择 5-氟尿嘧啶(5-FU)作为样品药物。负载 5-FU 的混合纳米凝胶呈球形,平均直径为 231.33±12.74nm,zeta 电位为-31.6mV。纳米凝胶的包封率和载药率分别为 42±4.52%和 2.37±0.59%。通过动态光散射(DLS)、傅里叶变换红外显微镜(FTIR)分析、场发射扫描电子显微镜(FE-SEM)和热重分析(TGA)对混合纳米凝胶的性能进行了分析。通过在不同缓冲液中 5-FU 的体外释放曲线证实了混合纳米凝胶的 pH 敏感性。溶血试验表明,混合纳米凝胶具有体外血液相容性,其对 MCF-7 细胞的 IC50 值为 16.21μM。本研究表明,这些基于生物的混合纳米凝胶在药物传递和其他生物医学应用中具有很大的潜力。

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