Antibody therapeutics contact a variety of interfaces from production through administration, and interfacial interactions can accelerate aggregation of these molecules, particularly under agitation stress immediately prior to administration when the product and the protective excipients are diluted. Due to the potential immunogenicity of antibody aggregates, a better understanding of the interfacial behavior of antibodies is desired and could assist during molecule selection as well as in the design of more robust formulations. Although many have studied the self-association of antibodies in solution, relatively little is known about their behavior when exposed to the hydrophobic environment at the air-water interface. We employ various surface-sensitive techniques to characterize the dynamics of antibodies directly at an air-water interface. Our recently developed confocal microscopy methodology quantifies the mass of antibody at the interface and can also measure the phase behavior and mobility of interfacially adsorbed molecules. Surface tensiometry, interfacial rheology, and an environmentally sensitive fluorophore assess the thermodynamic stability, mechanical properties, and molecular conformation of the adsorbed antibody films. In addition, the competitive adsorption of a weakly surface active polymer allows us to slow the antibody adsorption kinetics to better characterize differences in adsorption and interfacial self-association between antibodies with differing paratopes. Relating the interfacial properties of a panel of antibodies to their propensity to aggregate due to interfacial stress may allow us to predict the interfacial susceptibility of a particular therapeutic earlier during development.

Dynamics of interfacial adsorption and self-association of antibody therapeutics

247th National Meeting (2014)

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