Tein Y Summer, Zhang Zhenhuan, Wagner Norman J
Center for Neutron Science, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States.
Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.
Langmuir. 2020 Jul 14;36(27):7814-7823. doi: 10.1021/acs.langmuir.0c00797. Epub 2020 Jul 6.
Interfacial stresses can destabilize therapeutic formulations containing monoclonal antibodies (mAbs), which is proposed to be a result of adsorption and aggregation at the air-water interface. To increase protein stability, pharmaceutical industries add surfactants, such as Polysorbate 20 (PS20), into protein formulations to minimize mAb adsorption at the interface but rarely quantify this process. We determine that mAb adsorption in surfactant-free solutions creates a monolayer with significant viscoelasticity, which can influence measurements of bulk mAb solution viscosity. In contrast, PS20 absorption leads to an interface with negligible interfacial viscosity that protects the air-water interface from mAb adsorption. These studies were performed through a combined study of surface tensiometry, interfacial rheology, capillary viscometry, and neutron reflectometry to determine the surface activity of a model surfactant, PS20, and mAb system, which can be useful for the successful formulation developments of biotherapeutics.
界面应力会使含有单克隆抗体（mAb）的治疗性制剂不稳定，这被认为是由于在空气-水界面处的吸附和聚集所致。为了提高蛋白质稳定性，制药行业会在蛋白质制剂中添加表面活性剂，如聚山梨酯20（PS20），以尽量减少mAb在界面处的吸附，但很少对这一过程进行量化。我们确定，在无表面活性剂的溶液中mAb的吸附会形成具有显著粘弹性的单分子层，这会影响本体mAb溶液粘度的测量。相比之下，PS20的吸附会导致界面的界面粘度可忽略不计，从而保护空气-水界面免受mAb吸附。这些研究是通过对表面张力测定法、界面流变学、毛细管粘度测定法和中子反射测量法进行联合研究来确定模型表面活性剂PS20和mAb系统的表面活性，这对于生物治疗药物的成功制剂开发可能是有用的。
