InterFace/Off: characterization of competitive adsorption of novel surfactants and proteins at the solid-liquid and oil-liquid interfaces.

Interfacial stress encountered by biopharmaceuticals is often opposed by employing surfactants in their formulations. Surfactants protect proteins from this stress by either shielding the interface or displacing adsorbed proteins. Most previous studies were dedicated to the air-liquid interface, and to characterize monoclonal antibodies or non-pharmaceutically relevant proteins in combination with established surfactants (polysorbates and poloxamer 188). Herein, we employ quartz crystal microbalance with dissipation (QCM-D) and tensiometry to investigate the adsorption behavior of established surfactants as well as the novel surfactants VEDS and VEDG-3.3 at the solid-liquid and silicon oil-liquid interfaces in presence and absence of three model biotherapeutics of different modalities. Our study shows that the individual adsorption behavior is molecule-dependent, as expected. When mixed either simultaneously (co-adsorption) or sequentially (shielding and displacement), both proteins and surfactants were detected to co-adsorb at the interface. Compared to the established surfactants, VEDS and VEDG-3.3 showed a slower adsorption followed by molecular rearrangements that resulted in a denser packing, supporting the mechanistic explanation of their favorable protein stabilization effect previously reported. Collectively, our results support the generation of a unified thermodynamic description of the adsorption of protein-surfactants mixtures in pharmaceutically-relevant conditions.