Aggregation of biopharmaceuticals in human plasma and human serum: implications for drug research and development
| Autor: | Mohammed Shameem, Tudor Arvinte, Sonia M. Gregory, Henryk Mach, Chakravarthy Nachu Narasimhan, Caroline Palais, Erin Green-Trexler |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Serum medicine.drug_class media_common.quotation_subject Immunology Plasma protein binding Sodium Chloride compatibility Monoclonal antibody Antibodies Monoclonal Humanized Serum binding administration Biopharmaceutics Plasma Report Microscopy Drug Discovery medicine Immunology and Allergy Humans Surface plasmon resonance skin and connective tissue diseases media_common Chromatography biology Chemistry aggregation Antibodies Monoclonal biopharmaceuticals Surface Plasmon Resonance Trastuzumab Infliximab Bevacizumab Glucose Human plasma biology.protein Immunotherapy Antibody Protein Multimerization Protein Binding |
| Zdroj: | mAbs |
| ISSN: | 1942-0870 |
| Popis: | Analytical methods based on light microscopy, 90° light-scattering and surface plasmon resonance (SPR) allowed the characterization of aggregation that can occur when antibodies are mixed with human plasma. Light microscopy showed that aggregates formed when human plasma was mixed with 5% dextrose solutions of Herceptin(®) (trastuzumab) or Avastin(®) (bevacizumab) but not Remicade(®) (infliximab). The aggregates in the plasma-Herceptin(®)-5% dextrose solution were globular, size range 0.5-9 μm, with a mean diameter of 4 μm. The aggregates in the plasma-Avastin(®)-5% dextrose samples had a mean size of 2 μm. No aggregation was observed when 0.9% NaCl solutions of Herceptin(®), Avastin(®) and Remicade(®) were mixed with human plasma. 90° light-scattering measurements showed that aggregates were still present 2.5 h after mixing Herceptin(®) or Avastin(®) with 5% dextrose-plasma solution. A SPR method was utilized to qualitatively describe the extent of interactions of surface-bound antibodies with undiluted human serum. Increased binding was observed in the case of Erbitux(®) (cetuximab), whereas no binding was measured for Humira(®) (adalimumab). The binding of sera components to 13 monoclonal antibodies was measured and correlated with known serum binding properties of the antibodies. The data presented in this paper provide analytical methods to study the intrinsic and buffer-dependent aggregation tendencies of therapeutic proteins when mixed with human plasma and serum. |
| Databáze: | OpenAIRE |
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