Monoclonal Antibody Interactions With Micro- and Nanoparticles: Adsorption, Aggregation, and Accelerated Stress Studies
Monoclonal Antibody Interactions With Micro- and Nanoparticles: Adsorption, Aggregation, and Accelerated Stress Studies
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DOI：
10.1002/jps.21768
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Randolph, Theodore W.
中科院分区：
文献类型：
--
作者：
Bee, Jared S.;Chiu, David;Randolph, Theodore W.
治疗性蛋白质暴露于各种润湿表面，这些润湿表面可能会脱落不溶性颗粒。在这项工作中，我们测量了单克隆抗体（mAb）对各种微粒的吸附，表征了吸附的mAb二级结构，并确定了吸附的可逆性。我们还开发并使用了正面荧光猝灭法来确定mAb的三级结构在吸附到玻璃、纤维素和二氧化硅上时是近天然的。对每种测试材料的初始吸附是快速的。在孵育研究期间，暴露于空气-水界面是聚集的重要原因，但与微粒的影响无关。与玻璃，纤维素，不锈钢，或Fe 2 O3微粒孵育给出了非常不同的结果。纤维素优先吸附溶液中的聚集体。玻璃和Fe 2 O3吸附mAb，但不引起聚集。吸附到不锈钢微粒是不可逆的，并导致孵育后出现可溶性聚集体。吸附在玻璃和纤维素上的mAb的二级结构是近天然的。我们建议，在这项工作中描述的协议可能是一个有用的preformulation应力筛选工具，以确定治疗性蛋白质的敏感性暴露于常见的表面在加工和储存过程中遇到的。(c)2009威利-利斯公司和美国药学协会药物科学杂志98：3218-3238，2009
Therapeutic proteins are exposed to various wetted surfaces that could shed subvisible particles. In this work we measured the adsorption of a monoclonal antibody (mAb) to various microparticles, characterized the adsorbed mAb secondary structure, and determined the reversibility of adsorption. We also developed and used a front-face fluorescence quenching method to determine that the mAb tertiary structure was near-native when adsorbed to glass, cellulose, and silica. Initial adsorption to each of the materials tested was rapid. During incubation studies, exposure to the air-water interface was a significant cause of aggregation but acted independently of the effects of microparticles. Incubations with glass, cellulose, stainless steel, or Fe2O3 microparticles gave very different results. Cellulose preferentially adsorbed aggregates from solution. Glass and Fe2O3 adsorbed the mAb but did not cause aggregation. Adsorption to stainless steel microparticles was irreversible, and caused appearance of soluble aggregates upon incubation. The secondary structure of mAb adsorbed to glass and cellulose was near-native. We suggest that the protocol described in this work could be a useful preformulation stress screening tool to determine the sensitivity of a therapeutic protein to exposure to common surfaces encountered during processing and storage. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3218-3238, 2009