Prediction of Protein Aggregation in High Concentration Protein Solutions Utilizing Protein-Protein Interactions Determined by Low Volume Static Light Scattering
| Autor: | Melanie Hofmann, Christian Weber, Henning Gieseler, Matthias Winzer |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Work (thermodynamics) Chromatography Chemistry Antibodies Monoclonal Pharmaceutical Science Nanotechnology Flory–Huggins solution theory Protein aggregation 030226 pharmacology & pharmacy Dynamic Light Scattering Protein–protein interaction Pharmaceutical Solutions Protein Aggregates 03 medical and health sciences Polysorbates 030104 developmental biology 0302 clinical medicine Virial coefficient Immunoglobulin G Protein Interaction Domains and Motifs Static light scattering Forecasting Macromolecule |
| Zdroj: | Journal of Pharmaceutical Sciences. 105:1819-1828 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2016.03.022 |
| Popis: | The development of highly concentrated protein formulations is more demanding than for conventional concentrations due to an elevated protein aggregation tendency. Predictive protein-protein interaction parameters, such as the second virial coefficient B22 or the interaction parameter kD, have already been used to predict aggregation tendency and optimize protein formulations. However, these parameters can only be determined in diluted solutions, up to 20 mg/mL. And their validity at high concentrations is currently controversially discussed. This work presents a μ-scale screening approach which has been adapted to early industrial project needs. The procedure is based on static light scattering to directly determine protein-protein interactions at concentrations up to 100 mg/mL. Three different therapeutic molecules were formulated, varying in pH, salt content, and addition of excipients (e.g., sugars, amino acids, polysorbates, or other macromolecules). Validity of the predicted aggregation tendency was confirmed by stability data of selected formulations. Based on the results obtained, the new prediction method is a promising screening tool for fast and easy formulation development of highly concentrated protein solutions, consuming only microliter of sample volumes. |
| Databáze: | OpenAIRE |
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