This work reports the ability of hydrogel coatings to protect therapeutic proteins from cavitation-induced aggregation caused by mechanical stress. Here, we show that polyacrylamide hydrogel coatings on container surfaces suppress mechanical shock-induced cavitation and the associated aggregation of intravenous immunoglobulin (IVIg). First, crosslinked polyacrylamide hydrogels were grown on the surfaces of borosilicate glass vials. Treatment with ultrasound showed that these hydrogel surfaces suppressed cavitation events to levels below those found for unfunctionalized borosilicate glass. Next, IVIg solutions were loaded into these vials and subjected to tumbling, horizontal shaking, and drop testing. Aggregation was quantified by bisANS fluorescence staining and particle counting by flow imaging microscopy (FIM). In all cases, the presence of polyacrylamide hydrogels on the vial surfaces reduced the amount of IVIg aggregation and the number of particulates. In addition, the polyacrylamide appeared to have a protective effect that prevented additional aggregates from forming at extended tumbling times. Finally, drop test studies showed that the polyacrylamide coatings suppressed detectable cavitation. This work reveals how even a simple hydrogel vial coating can have a profound effect on stabilizing protein therapeutics.

中文翻译：

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容器表面的水凝胶涂层可减少由机械应力和空化引起的蛋白质聚集

这项工作报告了水凝胶涂层保护治疗性蛋白质免受机械应力引起的空化诱导聚集的能力。在这里，我们表明容器表面的聚丙烯酰胺水凝胶涂层可抑制机械冲击引起的空化和静脉内免疫球蛋白 (IVIg) 的相关聚集。首先，交联聚丙烯酰胺水凝胶在硼硅酸盐玻璃小瓶的表面上生长。用超声波处理表明，这些水凝胶表面将空化事件抑制到低于非功能化硼硅酸盐玻璃的水平。接下来，将 IVIg 溶液装入这些小瓶中，并进行翻滚、水平摇动和跌落测试。通过 bisANS 荧光染色和流动成像显微镜 (FIM) 的粒子计数来量化聚集。在所有情况下，小瓶表面上聚丙烯酰胺水凝胶的存在减少了IVIg聚集的量和微粒的数量。此外，聚丙烯酰胺似乎具有保护作用，可防止在延长的翻滚时间下形成额外的聚集体。最后，跌落试验研究表明聚丙烯酰胺涂层抑制了可检测到的空化。这项工作揭示了即使是简单的水凝胶小瓶涂层也可以对稳定蛋白质治疗产生深远的影响。跌落测试研究表明，聚丙烯酰胺涂层抑制了可检测到的气蚀。这项工作揭示了即使是简单的水凝胶小瓶涂层也可以对稳定蛋白质治疗产生深远的影响。跌落测试研究表明，聚丙烯酰胺涂层抑制了可检测到的气蚀。这项工作揭示了即使是简单的水凝胶小瓶涂层也可以对稳定蛋白质治疗产生深远的影响。