Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies
| Autor: | Jack F. Douglas, Sean Nugent, Jai A. Pathak, Robin J. Curtis, Christopher J. Roberts, Michael F. Bender |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Polymers and Plastics
Globular protein second virial coefficient Huggins coefficient Thermodynamics 02 engineering and technology static light scattering Article lcsh:QD241-441 03 medical and health sciences Viscosity lcsh:Organic chemistry Static light scattering flexible polymers 030304 developmental biology adhesive hard spheres chemistry.chemical_classification 0303 health sciences Chemistry Intermolecular force Solvation General Chemistry Hard spheres 021001 nanoscience & nanotechnology Virial coefficient monoclonal antibody intrinsic viscosity hard spheres Excluded volume viscosity 0210 nano-technology |
| Zdroj: | Polymers, Vol 13, Iss 601, p 601 (2021) Polymers Volume 13 Issue 4 |
| ISSN: | 2073-4360 |
| Popis: | The Huggins coefficient kH 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 kH measurements have been reported for select monoclonal antibodies (mAbs) solutions, there has been limited study of kH 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 kHfor 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 kH 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 kH from the standpoint of fundamental protein–protein interactions. Despite shortcomings in our theoretical understanding of kH 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. |
| Databáze: | OpenAIRE |
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