Hartl, Josef and Friesen, Sergej and Johannsmann, Diethelm and Buchner, Richard and Hinderberger, Dariush and Blech, Michaela and Garidel, Patrick (2022) Dipolar Interactions and Protein Hydration in Highly Concentrated Antibody Formulations. MOLECULAR PHARMACEUTICS, 19 (2). pp. 494-507. ISSN 1543-8384, 1543-8392
Full text not available from this repository. (Request a copy)Abstract
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 selfassembling 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, A2, the diffusion interaction parameter, kD, the elastic shear modulus, G', and the dynamic viscosity,.. When large contributions of dipolar protein-protein interactions were observed, the tendency of self-assembling and an increase in solution viscosity were detected. These effects were examined using specific buffer conditions. Furthermore, different types of protein-water interactions were identified via DRS, whereby the effect of high protein concentration on protein hydration was investigated for different high-concentrated liquid formulations (HCLFs).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIELECTRIC-RELAXATION SPECTROSCOPY; MONOCLONAL-ANTIBODY; VIRIAL-COEFFICIENTS; VISCOSITY; PREDICTION; WATER; AGGREGATION; ASSOCIATION; MODULATION; MECHANISMS; protein-protein interactions; monoclonal antibody; dipolar interaction; protein hydration |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry VI - Physical Chemistry (Solution Chemistry) > PD Dr. Richard Buchner |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Feb 2024 10:14 |
| Last Modified: | 16 Feb 2024 10:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58041 |
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