Small scale model for predicting transportation-induced particle formation in biotherapeutics

IF 5.4 2区 医学 Q1 BIOPHYSICS Colloids and Surfaces B: Biointerfaces Pub Date : 2024-10-09 DOI:10.1016/j.colsurfb.2024.114304
Urška Pečarič Strnad , Petra Zalokar , Natan Osterman , Mitja Zidar
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Abstract

Understanding protein adsorption and aggregation at the air-liquid interfaces of protein solutions is an important open challenge in biopharmaceutical, medical, and biotechnological applications, among others. Proteins, being amphiphilic, adsorb at the surface, partially unfold, and form a viscoelastic film through non-covalent interactions. Mechanical agitation of the surface can break this film up, releasing insoluble protein particles into the solution. These aggregates are usually highly undesirable and even toxic in cases, such as for biopharmaceutical application. Therefore, it is imperative to be able to predict the behavior of such solutions undergoing surface agitation during handling, usually transport or mixing. We apply the findings on the viscoelastic protein film, formed at the air-liquid interface, to the prediction of surface mediated aggregation in selected protein solutions of direct biopharmaceutical relevance. Our broad study of Brewster angle microscopy and aggregation monitoring across multiple size ranges by micro-flow imaging, light scattering, and size exclusion chromatography shows that formation of protein particles is driven by the adsorption rate as compared to the rate of surface turnover and that surface film dynamics in the quiescent phase directly affect aggregation. We demonstrate how these learnings can be directly applied to the design of a novel small scale biopharmaceutical stability study, simulating relevant transport conditions. More generally, we show the impact of adsorption dynamics at the air-liquid interface on the stability of a distinct protein solution, as a general contribution to understanding different colloidal and biological interfacial systems.
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预测生物治疗药物中运输诱导颗粒形成的小规模模型
了解蛋白质溶液在气液界面的吸附和聚集是生物制药、医疗和生物技术应用等领域的一项重要挑战。蛋白质具有两亲性,会吸附在表面,部分展开,并通过非共价作用形成一层粘弹性薄膜。对表面的机械搅拌会破坏这层薄膜,将不溶性蛋白质颗粒释放到溶液中。这些聚集体通常非常不受欢迎,在生物制药应用等情况下甚至会产生毒性。因此,必须能够预测此类溶液在处理(通常是运输或混合)过程中受到表面搅拌的行为。我们将在空气-液体界面形成的粘弹性蛋白质膜的研究成果应用于预测与生物制药直接相关的特定蛋白质溶液中由表面介导的聚集。我们通过微流成像、光散射和尺寸排除色谱法对布鲁斯特角显微镜和多种尺寸范围的聚集监测进行了广泛研究,结果表明,与表面周转率相比,蛋白质颗粒的形成是由吸附率驱动的,静止阶段的表面膜动态直接影响聚集。我们展示了如何将这些知识直接应用于设计新颖的小规模生物制药稳定性研究,模拟相关的运输条件。更广泛地说,我们展示了气液界面吸附动力学对不同蛋白质溶液稳定性的影响,这对理解不同胶体和生物界面系统具有普遍意义。
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来源期刊
Colloids and Surfaces B: Biointerfaces
Colloids and Surfaces B: Biointerfaces 生物-材料科学:生物材料
CiteScore
11.10
自引率
3.40%
发文量
730
审稿时长
42 days
期刊介绍: Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.
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