Probing Molecular Interactions of Antibody Drugs, Silicone Oil, and Surfactant at Buried Interfaces In Situ

被引:3
作者
Lu, Tieyi [1 ]
Fu, Li [2 ]
Qiu, Yu [3 ]
Zhang, Jifeng [2 ]
Chen, Zhan [1 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[2] Sanofi, Framingham, MA 01701 USA
[3] Sanofi, Cambridge, MA 02141 USA
关键词
AMIDE-I; PROTEINS; PEPTIDES; ADSORPTION; DYNAMICS;
D O I
10.1021/acs.analchem.2c03425
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Antibody drugs have been rapidly developed to cure many diseases including COVID-19 infection. Silicone oil is commonly used as a lubricant coating material for devices used in the pharmaceutical industry to store and administer antibody drug formulations. However, the interaction between silicone oil and antibody molecules could lead to the adsorption, denaturation, and aggregation of antibody molecules, impacting the efficacy of antibody drugs. Here, we studied the molecular interactions between antibodies and silicone oil in situ in real time. The effect of the surfactant on such interactions was also investigated. Specifically, the adsorption dynamics of a bispecific antibody (BsAb) onto a silicone oil surface without and with different concentrations of the surfactant PS80 in antibody solutions were monitored. Also the possible lowest effective PS80 concentrations that can prevent the adsorption of BsAb as well as a monoclonal antibody (mAb) onto silicone oil were measured. It was found that different concentrations of PS80 are required for preventing the adsorption of different antibodies. Both BsAB and mAB denature on silicone oil without a surfactant. However, for a low surfactant concentration in the solution, although the surfactant could not completely prevent the antibody from adsorption, it could maintain the native structures of adsorbed BsAb and mAb antibodies on silicone oil. This is important knowledge, showing that to prevent antibody aggregation on silicone oil it is not necessary to add surfactant to a concentration high enough to completely minimize protein adsorption.
引用
收藏
页码:14761 / 14768
页数:8
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