Armoring the interface with surfactant to prevent the adsorption of monoclonal antibody.

The pharmaceutical industry uses surface active-agents (excipients) in protein drug formulations to prevent aggregation, denaturation, and unwanted immunological response of therapeutic drugs in solution as well as at the air/water interface. However, the mechanism of adsorption, desorption and aggregation of proteins at the interface in the presence of excipients remains poorly understood. The objective of this work is to explore the molecular scale competitive adsorption process between surfactant-based excipients and two monoclonal antibody (mAb) proteins, mAb-1 and mAb-2. We use pendant bubble tensiometry to measure the ensemble average adsorption dynamics of mAbs with and without the excipient. The surface tension measurements allows us to quantify the rate at which the molecules ``race'' to the interface in single component and mixed systems. These results define the phase space where co-adsorption of both mAbs and excipients occurs onto the air/water interface. In parallel, we use X-ray reflectivity (XR) measurements to understand the molecular scale dynamics of competitive adsorption, revealing the surface adsorbed amounts of antibody and excipient. XR has revealed that at sufficiently high surface concentration of excipient, mAb adsorption to the surface and sub-surface domain was inhibited. In addition, despite the fact that both mAbs adsorb via a similar mechanistic pathway and with similar dynamics, a key finding is that the competition for the interface directly correlates with the surface activity of the two mAbs, resulting in a five-fold difference in the concentration of excipient needed to displace the antibody.