title: Gauging colloidal and thermal stability in human IgG1-sugar solutions through diffusivity measurements.
abstract: Monoclonal 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.
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology , Atlanta, Georgia 30332-0100, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
authors.forename: Aditi
authors.initials: A
authors.lastname: Sharma
authors.forename: Lars
authors.initials: L
authors.lastname: Linden
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Bommarius
authors.forename: Sven H
authors.initials: SH
authors.lastname: Behrens
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D002942:Circular Dichroism; D003102:Colloids / Q000737:chemistry; D004058:Diffusion; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008958:Models, Molecular; D055550:Protein Stability; D012996:Solutions; D013696:Temperature; D013997:Time Factors
chemical_list: D002241:Carbohydrates; D003102:Colloids; D007074:Immunoglobulin G; D012996:Solutions