报告人：Prof Gerald Fuller，Chemical Engineering, Stanford University, Stanford, CA 94305
时间：2018年12月5日（周三）10：00
地点： 广州市番禺区大学城外环西路230号，广州大学计算机实验楼709会议室
摘要：Monoclonal antibodies (mAbs) are therapeutic proteins used in the treatment of many diseases due to their specificity in identifying pathogens. Aggregation of these antibody molecules is a major challenge in their formulation development. One of the primary causes of aggregation is the surface activity of mAbs that makes them spontaneously adsorb onto air-solution interfaces and experience interfacial stresses. This work studies the effect of different pharmaceutically relevant surfactants like polysorbate-20, poloxamer-188 and polyethylene glycol in controlling the bulk aggregation and interfacial behavior. Aggregation through controlled agitation was characterized using size-exclusion chromatography, flow cytometry and light obscuration. The addition of surfactants reduced the formation of aggregates of different sizes. In the presence of surfactants competitively adsorbing to the interface, the number of smaller, soluble aggregates (<100 nm) depended on the amount of mAbs adsorbed at the interface. On the other hand, the amount of larger, insoluble aggregates was governed not by the surface concentration, but the ability of the adsorbed mAbs to interact and form a cohesive network. To correlate the aggregation in these mAb-surfactant mixtures with their behavior at air-solution interfaces, studies on the drainage of a fluid film sandwiched between two mAb-surfactant laden interfaces were performed. The amount of fluid entrained depended on different governing mechanisms – interfacial rheology, surface tension and surface tension gradients for different surfactants. The surface tension gradients further resulted in an instability and local thickening in the sandwiched fluid film, which was affected by the presence of mAbs. Understanding the aggregation propensities of different mAb-surfactant mixtures and linking them to the interfacial behavior will greatly aid in understanding the mechanism of aggregation and designing better formulations.
