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Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies.

ABSTRACT: The Huggins coefficient k_H is a well-known metric for quantifying the increase in solution viscosity arising from intermolecular interactions in relatively dilute macromolecular solutions, and there has been much interest in this solution property in connection with developing improved antibody therapeutics. While numerous k_H measurements have been reported for select monoclonal antibodies (mAbs) solutions, there has been limited study of k_H in terms of the fundamental molecular interactions that determine this property. In this paper, we compare measurements of the osmotic second virial coefficient B₂₂, a common metric of intermolecular and interparticle interaction strength, to measurements of k_H for model antibody solutions. This comparison is motivated by the seminal work of Russel for hard sphere particles having a short-range "sticky" interparticle interaction, and we also compare our data with known results for uncharged flexible polymers having variable excluded volume interactions because proteins are polypeptide chains. Our observations indicate that neither the adhesive hard sphere model, a common colloidal model of globular proteins, nor the familiar uncharged flexible polymer model, an excellent model of intrinsically disordered proteins, describes the dependence of k_H of these antibodies on B₂₂. Clearly, an improved understanding of protein and ion solvation by water as well as dipole-dipole and charge-dipole effects is required to understand the significance of k_H from the standpoint of fundamental protein-protein interactions. Despite shortcomings in our theoretical understanding of k_H for antibody solutions, this quantity provides a useful practical measure of the strength of interprotein interactions at elevated protein concentrations that is of direct significance for the development of antibody formulations that minimize the solution viscosity.

SUBMITTER: Pathak JA

PROVIDER: S-EPMC7922252 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies.

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