Characterization of highly concentrated antibody solution - A toolbox for the description of protein long-term solution stability
| Autor: | Jürgen Hubbuch, Michel H.M. Eppink, Marie Therese Schermeyer, Anna Katharina Wöll, Bas Kokke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Conformational and colloidal stability Bio Process Engineering Immunology 02 engineering and technology Stability (probability) thermal stability 03 medical and health sciences Viscosity chemistry.chemical_compound Drug Stability Report Zeta potential Immunology and Allergy Thermal stability viscoelasticity VLAG Molecular interactions Chromatography Protein Stability Antibodies Monoclonal 021001 nanoscience & nanotechnology Characterization (materials science) phase diagram Formulation stability 030104 developmental biology Monomer chemistry viscosity monoclonal antibodies zeta-potential 0210 nano-technology Biological system |
| Zdroj: | mAbs mAbs 9 (2017) 7 mAbs, 9(7), 1169-1185 |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | High protein titers are gaining importance in biopharmaceutical industry. A major challenge in the development of highly concentrated mAb solutions is their long-term stability and often incalculable viscosity. The complexity of the molecule itself, as well as the various molecular interactions, make it difficult to describe their solution behavior. To study the formulation stability, long- and short-range interactions and the formation of complex network structures have to be taken into account. For a better understanding of highly concentrated solutions, we combined established and novel analytical tools to characterize the effect of solution properties on the stability of highly concentrated mAb formulations. In this study, monoclonal antibody solutions in a concentration range of 50–200 mg/ml at pH 5–9 with and without glycine, PEG4000, and Na2SO4 were analyzed. To determine the monomer content, analytical size-exclusion chromatography runs were performed. ζ-potential measurements were conducted to analyze the electrophoretic properties in different solutions. The melting and aggregation temperatures were determined with the help of fluorescence and static light scattering measurements. Additionally, rheological measurements were conducted to study the solution viscosity and viscoelastic behavior of the mAb solutions. The so-determined analytical parameters were scored and merged in an analytical toolbox. The resulting scoring was then successfully correlated with long-term storage (40 d of incubation) experiments. Our results indicate that the sensitivity of complex rheological measurements, in combination with the applied techniques, allows reliable statements to be made with respect to the effect of solution properties, such as protein concentration, ionic strength, and pH shift, on the strength of protein-protein interaction and solution colloidal stability. |
| Databáze: | OpenAIRE |
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