Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
Materials Science and Engineering Program, University of Colorado Boulder, Boulder, CO, 80303, USA.
Biotechnol J. 2020 Sep;15(9):e2000096. doi: 10.1002/biot.202000096. Epub 2020 Jun 8.
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. How different mechanical stress conditions (dropping, tumbling, and agitation) and container surface passivation affect the stability of solutions of intravenous immunoglobulin are investigated. Application of mechanical shock causes 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. Cavitation was observed after dropping of vials from heights as low as 5 cm, but polyethylene glycol (PEG) grafting provided temporary protection against drop-induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates 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 and/or mechanical shock.
蛋白质的聚集可能是由于在制造、运输和储存过程中遇到的许多应激条件造成的。这项工作研究了两种相关的蛋白质聚集源的影响：蛋白质储存容器的表面化学性质和结构，以及制剂处理可能导致的机械冲击。研究了不同的机械应力条件（跌落、翻滚和搅拌）和容器表面钝化如何影响静脉注射免疫球蛋白溶液的稳定性。机械冲击会导致蛋白质溶液中发生空化，随后气泡坍塌并形成高速流体微射流，冲击容器表面，导致颗粒形成。从 5 厘米的高度跌落就可以观察到空化现象，但聚乙二醇（PEG）接枝提供了暂时的保护，防止跌落引起的空化。聚乙二醇处理容器表面减少了反复跌落事件后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来实现的。这些研究为开发新的涂层和表面化学提供了可能，这些涂层和表面化学可以减少表面吸附和/或机械冲击引起的颗粒形成。
