Stress Tolerance of Antibody–Poly(Amino Acid) Complexes for Improving the Stability of High Concentration Antibody Formulations
| Autor: | Tomoaki Kimoto, Kenji Handa, Izaki Shunsuke, Takaaki Kurinomaru, Kentaro Shiraki |
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| Rok vydání: | 2015 |
| Předmět: |
Hot Temperature
genetic structures Chemistry Pharmaceutical Drug Storage Pharmaceutical Science Omalizumab behavioral disciplines and activities Suspension (chemistry) Stress (mechanics) Protein Aggregates Drug Stability Suspensions Animals Chemical Precipitation Humans Anti-Asthmatic Agents Particle Size Dissolution chemistry.chemical_classification Chromatography Aqueous solution biology Protein Stability Precipitation (chemistry) Chemistry Preservatives Pharmaceutical Adalimumab Antibodies Monoclonal Polyelectrolyte Amino acid body regions Models Chemical Pharmaceutical Preparations Polyglutamic Acid Solubility nervous system Antirheumatic Agents biology.protein Stress Mechanical Antibody psychological phenomena and processes |
| Zdroj: | Journal of Pharmaceutical Sciences. 104:2457-2463 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.24515 |
| Popis: | The stabilization of antibodies in aqueous solution against physical stress remains a problematic issue for pharmaceutical applications. Recently, protein-polyelectrolyte complex (PPC) formation using poly(amino acids) was proposed to prepare antibody formulation in a salt-dissociable precipitated state without protein denaturation. Here, we investigated the stabilization effect of PPC of therapeutic antibodies with poly-l-glutamic acid on agitation and thermal stress as forms of mechanical and non-mechanical stress, respectively. The precipitated state of PPC prevented the inactivation and aggregation induced by agitation. Similar results were obtained using the suspension state of PPC, but the stabilizing effects were slightly inferior to those of the PPC precipitate. PPC precipitate and PPC suspension prevented heat-induced inactivation of the antibodies, but showed little effect on heat-induced aggregation. Thus, PPC is a new candidate as a simple storage method for antibodies in aqueous solution, as an alternative state for freeze-drying. |
| Databáze: | OpenAIRE |
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