The Effect of Container Surface Passivation on Aggregation of Intravenous Immunoglobulin Induced by Mechanical Shock.
The Effect of Container Surface Passivation on Aggregation of Intravenous Immunoglobulin Induced by Mechanical Shock.
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DOI：
10.1002/biot.202000096
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发表时间：
2020-09
影响因子：
4.7
通讯作者：
Goodwin AP
中科院分区：
文献类型：
--
作者：
Movafaghi S;Wu H;Francino Urdániz IM;Bull DS;Kelly MD;Randolph TW;Goodwin AP
治疗性蛋白质的聚集可能是由于它们在制造、运输和储存过程中遇到的一些应激条件造成的。这项工作显示了蛋白质聚集的两个相互关联的来源的影响：储存蛋白质的容器表面的化学和结构，以及处理配方可能导致的机械冲击。我们研究了不同的机械应力条件(滴落、翻滚和搅拌)和容器表面钝化对静脉注射免疫球蛋白(IVIG)溶液稳定性的影响。应用机械冲击导致蛋白质溶液中发生空化，随后气泡破裂，形成冲击容器表面的高速流体微喷流，导致颗粒形成。我们还观察到小瓶从5厘米的高度掉落后产生的空化，聚乙二醇接枝可以提供暂时的保护，防止滴状诱导的空化。瓶子表面的聚乙二醇酯处理减少了反复滴落事件后观察到的蛋白质聚集体的形成，这很可能是通过减少蛋白质对容器表面的吸附而实现的。这些研究使新涂层和表面化学的开发成为可能，它们可以减少表面吸附或/和机械冲击引起的颗粒形成。
Aggregation of therapeutic proteins can result from a number of stress conditions encountered during their manufacture, transportation, and storage. This work shows the effects of two interrelated sources of protein aggregation: the chemistry and structure of the surface of the container in which the protein is stored, and mechanical shocks that may result from handling of the formulation. We investigated how different mechanical stress conditions (dropping, tumbling and agitation) and container surface passivation affected the stability of solutions of intravenous immunoglobulin (IVIG). Application of mechanical shock caused cavitation to occur in the protein solution, followed by bubble collapse and the formation of high-velocity fluid microjets that impinged on container surfaces, leading to particle formation. We also observed cavitation following dropping of vials from heights as low as 5 cm and that polyethylene glycol (PEG) grafting could provide temporary protection against drop-induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates observed after repeated dropping events, most likely by reducing protein adsorption to container surfaces. These studies enable the development of new coatings and surface chemistries that can reduce the particulate formation induced by surface adsorption or/and mechanical shock.
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影响因子：
3.9
作者：
Halperin, A
通讯作者：
Halperin, A
影响因子：
3.8
作者：
Bee, Jared S.;Chiu, David;Randolph, Theodore W.
通讯作者：
Randolph, Theodore W.
影响因子：
3.7
作者：
Hawe, Andrea;Sutter, Marc;Jiskoot, Wim
通讯作者：
Jiskoot, Wim
影响因子：
2.7
作者：
BURCKHARDT, JJ;GARDI, A;HEINIGER, HJ
通讯作者：
HEINIGER, HJ
影响因子：
3.3
作者：
Emmi, L;Chiarini, F
通讯作者：
Chiarini, F