切向流过滤促进聚合人血清白蛋白的分馏:洞察分子大小对生物物理特性的影响。

IF 2.5 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Amna Abdalbaqi, Ahmad Yahya, Krianthan Govender, Carlos Muñoz, Gala Sanchez Van Moer, Daniela Lucas, Pedro Cabrales, Andre F Palmer
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引用次数: 0

摘要

目前,人血清白蛋白(HSA)被用作血浆膨胀剂(PE),用于在失血等低血容量情况下增加血容量。然而,由于脓毒性休克和烧伤患者的内皮通透性增强,导致 HSA 外渗至组织间隙引起水肿,以及 HSA 结合的有毒代谢物沉积,因此在这些患者中使用 HSA 的效果并不理想。因此,为了扩大 HSA 在治疗内皮通透性受损患者方面的适用性,以前曾对 HSA 进行过聚合,以增加其分子大小,从而将聚合的 HSA(PolyHSA)分子分隔在血管空间中。以前的研究将 PolyHSA 定义为 100 kDa 至 0.2 μm。在这项研究中,PolyHSA 是以 43:1 和 60:1 两种交联密度(即戊二醛与 HSA 的摩尔比)合成的,随后通过切向流过滤 (TFF) 分馏成两个较窄的支架:支架 A(500 kDa 和 0.2 μm)和支架 B(50-500 kDa)。在不同交联密度下,同一粒度范围内的 PolyHSA 表现出相似的溶液粘度、ZETA 电位和渗透压,但流体力学直径不同。在相同的交联密度下,PolyHSA A bracket 与 PolyHSA B bracket 相比,在保持渗透压的情况下,粘度更高,zeta 电位更低,水动力直径更大。有趣的是,PolyHSA 43:1 B、PolyHSA 60:1 A 和 PolyHSA 60:1 B 托架显示出与 HSA 相似的胶体渗透压,这表明它们具有作为 PE 的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tangential flow filtration facilitated fractionation of polymerized human serum albumin: Insights into the effects of molecular size on biophysical properties.

Human serum albumin (HSA) is currently used as a plasma expander (PE) to increase blood volume during hypovolemic conditions, such as blood loss. However, its effectiveness is suboptimal in septic shock and burn patients due to their enhanced endothelial permeability, resulting in HSA extravasation into the tissue space leading to edema, and deposition of toxic HSA-bound metabolites. Hence, to expand HSA's applicability toward treating patients with compromised endothelial permeability, HSA has been previously polymerized to increase its molecular size thus compartmentalizing the polymerized HSA (PolyHSA) molecules in the vascular space. Previous studies bracketed PolyHSA between 100 kDa and 0.2 μm. In this research, PolyHSA was synthesized at two cross-link densities 43:1 and 60:1 (i.e., molar ratios of glutaraldehyde to HSA) and subsequently fractionated via tangential flow filtration (TFF) into two narrower brackets: bracket A (500 kDa and 0.2 μm) and bracket B (50-500 kDa). PolyHSA within the same size bracket at different cross-link densities exhibited similar solution viscosity, zeta potential, and osmolality but differed in hydrodynamic diameter. At the same cross-link density, the PolyHSA A bracket showed higher viscosity, lowered zeta potential, and a larger hydrodynamic diameter compared with the PolyHSA B bracket while maintaining osmolality. Interestingly, PolyHSA 43:1 B, PolyHSA 60:1 A, and PolyHSA 60:1 B brackets exhibited colloid osmotic pressure similar to HSA, indicating their potential to serve as PEs.

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来源期刊
Biotechnology Progress
Biotechnology Progress 工程技术-生物工程与应用微生物
CiteScore
6.50
自引率
3.40%
发文量
83
审稿时长
4 months
期刊介绍: Biotechnology Progress , an official, bimonthly publication of the American Institute of Chemical Engineers and its technological community, the Society for Biological Engineering, features peer-reviewed research articles, reviews, and descriptions of emerging techniques for the development and design of new processes, products, and devices for the biotechnology, biopharmaceutical and bioprocess industries. Widespread interest includes application of biological and engineering principles in fields such as applied cellular physiology and metabolic engineering, biocatalysis and bioreactor design, bioseparations and downstream processing, cell culture and tissue engineering, biosensors and process control, bioinformatics and systems biology, biomaterials and artificial organs, stem cell biology and genetics, and plant biology and food science. Manuscripts concerning the design of related processes, products, or devices are also encouraged. Four types of manuscripts are printed in the Journal: Research Papers, Topical or Review Papers, Letters to the Editor, and R & D Notes.
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