不同等级聚山梨醇酯 20 和 80 与蛋白质-敷料相互作用的热力学研究

IF 3 3区 工程技术 Q2 CHEMISTRY, ANALYTICAL
Joseph Whiteley, Laura J. Waters, James Humphrey, Steve Mellor
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引用次数: 0

摘要

开发稳定的生物制药配方至关重要,通常需要加入表面活性剂作为稳定剂,如聚山梨醇酯 20 和 80。然而,人们对表面活性剂等级对制剂稳定性的影响知之甚少。本研究使用等温滴定量热法(ITC)和差示扫描量热法(DSC)评估了普通级和超精制™级聚山梨醇酯 20 和 80 的效果及其与模型蛋白质(即 β-乳球蛋白(β-Ig)、人血清白蛋白(HSA)和γ 免疫球蛋白(IgG))的相互作用。ITC 结果表明,所有四种聚山梨醇酯都与β-Ig 和 HSA 发生了结合相互作用,但与 IgG 却没有发生相互作用,这可能是二级结构组成不同的结果。无论使用哪种表面活性剂,表面活性剂与 β-Ig 的结合比例均为 3:2,解离常数为 284 至 388 µM,而与 HSA 的结合比例为 3:1,解离常数为 429 至 653 µM。与 β-Ig 相比,表面活性剂与 HSA 的相互作用焓变更大,这意味着前者比后者产生了更大的结合相互作用。DSC 测量了每种蛋白质在每种聚山梨醇酯存在下的解折温度,结果进一步证实,β-Ig 和 HSA 发生了相互作用,解折温度在 4 至 6 K 之间升高,这意味着蛋白质的稳定性有所提高,但同样没有观察到 IgG 发生相互作用。本研究从热力学角度描述了聚山梨醇酯在生物制药配方中稳定蛋白质的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A thermodynamic investigation into protein–excipient interactions involving different grades of polysorbate 20 and 80

A thermodynamic investigation into protein–excipient interactions involving different grades of polysorbate 20 and 80

Developing stable biopharmaceutical formulations is of paramount importance and is typically achieved by incorporating surfactants as stabilising agents, such as polysorbate 20 and 80. However, little is known about the effect surfactant grade has on formulation stability. This study evaluates the effect of regular grade and Super-refined™ polysorbates 20 and 80 and their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) and immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). ITC results indicated that all four polysorbates underwent binding interactions with β-Ig and HSA, yet no interaction was observed with IgG this is postulated to be a consequence of differences in secondary structure composition. Surfactant binding to β-Ig occurred at ratios of ~ 3:2 regardless of the surfactant used with dissociation constants ranging from 284 to 388 µM, whereas HSA bound at ratios of ~ 3:1 and dissociation constants ranging from 429 to 653 µM. Changes in enthalpy were larger for the surfactant interactions with HSA compared with β-Ig implying the former produced a greater binding interaction than the latter. DSC facilitated measurement of the temperature of unfolding of each protein with the presence of each polysorbate where results further confirmed interactions had occurred for β-Ig and HSA with an increased unfolding temperature between 4 and 6 K implying improved protein stability, yet again, no interaction was observed with IgG. This study thermodynamically characterised the role of polysorbates in protein stabilisation for biopharmaceutical formulations.

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来源期刊
CiteScore
8.50
自引率
9.10%
发文量
577
审稿时长
3.8 months
期刊介绍: Journal of Thermal Analysis and Calorimetry is a fully peer reviewed journal publishing high quality papers covering all aspects of thermal analysis, calorimetry, and experimental thermodynamics. The journal publishes regular and special issues in twelve issues every year. The following types of papers are published: Original Research Papers, Short Communications, Reviews, Modern Instruments, Events and Book reviews. The subjects covered are: thermogravimetry, derivative thermogravimetry, differential thermal analysis, thermodilatometry, differential scanning calorimetry of all types, non-scanning calorimetry of all types, thermometry, evolved gas analysis, thermomechanical analysis, emanation thermal analysis, thermal conductivity, multiple techniques, and miscellaneous thermal methods (including the combination of the thermal method with various instrumental techniques), theory and instrumentation for thermal analysis and calorimetry.
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