Dipolar Interactions and Protein Hydration in Highly Concentrated Antibody Formulations
| Autor: | Josef Hartl, Sergej Friesen, Diethelm Johannsmann, Richard Buchner, Dariush Hinderberger, Michaela Blech, Patrick Garidel |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Molecular Pharmaceutics. 19:494-507 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | Molecular interaction mechanisms in high-concentrated protein systems are of fundamental importance for the rational development of biopharmaceuticals such as monoclonal antibody (mAb) formulations. In such high-concentrated protein systems, the intermolecular distances between mAb molecules are reduced to the size of the protein diameter (approx. 10 nm). Thus, protein-protein interactions are more pronounced at high concentrations; so a direct extrapolation of physicochemical properties obtained from measurements at a low protein concentration of the corresponding properties at a high protein concentration is highly questionable. Besides the charge-charge interaction, the effects of molecular crowding, dipolar interaction, changes in protein hydration, and self-assembling tendency become more relevant. Here, protein hydration, protein dipole moment, and protein-protein interactions were studied in protein concentrations up to 200 mg/mL (= 1.3 mM) in different formulations for selected mAbs using dielectric relaxation spectroscopy (DRS). These data are correlated with the second virial coefficient |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|