Experimental Model System to Study pH Shift-Induced Aggregation of Monoclonal Antibodies Under Controlled Conditions
| Autor: | Olubukayo-Opeyemi Oyetayo, Hans Kiefer |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Protein Denaturation Protein Folding Protein Conformation Drug Compounding Kinetics Protein Renaturation Pharmaceutical Science Trimethylamine Protein aggregation 030226 pharmacology & pharmacy Catalysis Absorbance Excipients 03 medical and health sciences chemistry.chemical_compound Methylamines Protein Aggregates Structure-Activity Relationship 0302 clinical medicine Drug Stability Technology Pharmaceutical Pharmacology (medical) Fluorometry Histidine Solubility Pharmacology Chromatography Chemistry Protein Stability Organic Chemistry Antibodies Monoclonal Trehalose Hydrogen-Ion Concentration 030104 developmental biology Models Chemical Molecular Medicine Biotechnology |
| Zdroj: | Pharmaceutical research. 33(6) |
| ISSN: | 1573-904X |
| Popis: | To present a convenient screening method for evaluating additive effects on the renaturation of an acid-exposed monoclonal antibody (mAb). The assay involves brief incubation of a mAb at acidic pH and subsequent neutralization in the absence or presence of additive to induce mainly aggregation. An increase in absorbance depicted aggregation. The recorded aggregation data traces were fitted with a nucleation-autocatalytic growth model for the extraction of kinetic parameters. All kinetic data traces were fitted successfully with the selected model and the adjusted R square values were greater than 0.99. Trehalose had strongly stabilizing, proline mildly stabilizing and trimethylamine oxide had destabilizing effects on both the nucleation and growth phase of the reaction. Histidine was strongly stabilizing but was limited by its poor solubility. The results demonstrate the suitability of the experimental mAb aggregation system and the nucleation-autocatalytic growth fit in the screening and quantification of additive effects on the renaturation of an acid-exposed mAb respectively. This will aid the investigation and derivation of quantitative structure-activity relationships of additive effects on mAb solubility. |
| Databáze: | OpenAIRE |
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