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Gauging Colloidal and Thermal Stability in Human IgG1–Sugar Solutions through Diffusivity Measurements
journal contribution
posted on 2014-03-20, 00:00 authored by Jonathan Rubin, Aditi Sharma, Lars Linden, Andreas
S. Bommarius, Sven H. BehrensMonoclonal
antibodies are the fastest growing class of biotherapeutics.
Ensuring their colloidal and conformational stability in liquid dispersions
is crucial for maintaining therapeutic efficacy and economic viability.
Sugars are often added to increase the colloidal and thermal stability
of protein; however, determining which sugar is the most stabilizing
requires time and sample-consuming stability tests. Here we show for
a human IgG1 that the extent of stabilization by different sugars
can be gauged by analyzing the proteins’ diffusive virial coefficient kD. This protein interaction
parameter is measured conveniently in a noninvasive, high-throughput
manner using dynamic light scattering. It is found to correlate closely
with experimental aggregation rate constants at the onset of aggregation
and with melting temperatures for antibodies in different sugar solutions.
The proposed analysis thus provides a rapid test of the subtle differences
between inherently similar sugar–protein interactions; it should
greatly facilitate the formulation of protein therapeutics. For the
antibody investigated in this study, circular dichroism spectroscopy
also yields clues about the mechanism by which sugars
improve the thermal stability.