Molecular Computations of Preferential Interaction Coefficients of IgG1 Monoclonal Antibodies with Sorbitol, Sucrose, and Trehalose and the Impact of These Excipients on Aggregation and Viscosity
Autor: | Hasige A. Sathish, Chaitanya Sudrik, Theresa K. Cloutier, Bernhardt L. Trout, Neil Mody |
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Rok vydání: | 2019 |
Předmět: |
Sucrose
Chemistry Pharmaceutical Drug Storage Pharmaceutical Science Excipient 02 engineering and technology Buffers Molecular Dynamics Simulation 030226 pharmacology & pharmacy Excipients Protein Aggregates 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Viscosity 0302 clinical medicine Drug Discovery medicine Sorbitol Antibodies Monoclonal Trehalose Carbohydrate 021001 nanoscience & nanotechnology Freeze Drying chemistry Immunoglobulin G Biophysics Molecular Medicine 0210 nano-technology Hydrophobic and Hydrophilic Interactions Sodium acetate medicine.drug |
Zdroj: | Molecular Pharmaceutics. 16:3657-3664 |
ISSN: | 1543-8392 1543-8384 |
Popis: | Preferential interactions of formulation excipients govern their overall interactions with protein molecules, and molecular dynamics simulations allow for the examination of the interactions at the molecular level. We used molecular dynamics simulations to examine the interactions of sorbitol, sucrose, and trehalose with three different IgG1 antibodies to gain insight into how these excipients impact aggregation and viscosity. We found that sucrose and trehalose reduce aggregation more than sorbitol because of their larger size and their stronger interactions with high-spatial aggregation propensity residues compared to sorbitol. Two of the antibodies had high viscosity in sodium acetate buffer, and for these, we found that sucrose and trehalose tended to have opposite effects on viscosity. The data presented here provide further insight into the mechanisms of interactions of these three carbohydrate excipients with the antibody surface and thus their impact on excipient stabilization of antibody formulations. |
Databáze: | OpenAIRE |
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