Advancing predictions of protein stability in the solid state
Advancing predictions of protein stability in the solid state
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DOI：
10.1039/d0cp00341g
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发表时间：
2020-08-14
影响因子：
3.3
通讯作者：
Van den Mooter, Guy
中科院分区：
文献类型：
--
作者：
Batens, Maarten;Shmool, Talia A.;Van den Mooter, Guy
与亚玻璃化转变温度(T-g，T-β)相关的β-松弛是由于分子在主玻璃化转变温度(T-g，T-α)以下发生的快速局域分子运动。与远低于储存温度观察到的(g，β)一致，β松弛相关运动被假设为影响蛋白质在固态中的稳定性，从而可能影响吸入或重组和注射用蛋白质粉的质量。那么，为什么干燥和立即重建后具有相似聚集特征的不同固态蛋白质配方在长期储存后重建时表现出不同的特征呢？与体系的β-松弛过程相关的t(g，β)值是表征蛋白质在固态中行为的可靠参数吗？考虑到这一点，在这项工作中，我们进一步探索了玻璃固态单抗制剂的不同松弛动力学，使用太赫兹时域光谱和动态力学分析。通过对一系列多组分喷雾干燥制剂进行52周的稳定性研究，概述了一种表征和分析固态动力学及其与蛋白质稳定性的关系的方法。
The beta-relaxation associated with the sub-glass transition temperature (T-g,T-beta) is attributed to fast, localised molecular motions which can occur below the primary glass transition temperature (T-g,T-alpha). Consistent withT(g,beta)being observed well-below storage temperatures, the beta-relaxation associated motions have been hypothesised to influence protein stability in the solid state and could thus impact the quality ofe.g.protein powders for inhalation or reconstitution and injection. Why then do distinct solid state protein formulations with similar aggregation profiles after drying and immediate reconstitution, display different profiles when reconstituted following prolonged storage? Is the value ofT(g,beta), associated with the beta-relaxation process of the system, a reliable parameter for characterising the behaviour of proteins in the solid state? Bearing this in mind, in this work we further explore the different relaxation dynamics of glassy solid state monoclonal antibody formulations using terahertz time-domain spectroscopy and dynamical mechanical analysis. By conducting a 52 week stability study on a series of multi-component spray-dried formulations, an approach for characterising and analysing the solid state dynamics and how these relate to protein stability is outlined.