Feasibility of Antibody–Poly(Glutamic Acid) Complexes: Preparation of High-Concentration Antibody Formulations and Their Pharmaceutical Properties
| Autor: | Izaki Shunsuke, Tomoaki Kimoto, Takaaki Kurinomaru, Takuya Maruyama, Takayuki Uchida, Kentaro Shiraki, Kenji Handa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
High concentration
chemistry.chemical_classification Circular dichroism Chromatography biology Adalimumab Anti-Inflammatory Agents Pharmaceutical Science Omalizumab Glutamic acid Protein Structure Secondary Rats Amino acid Polyglutamic Acid chemistry Pharmacokinetics Toxicity biology.protein Animals Chemical Precipitation Humans Anti-Asthmatic Agents Antibody Protein secondary structure |
| Zdroj: | Journal of pharmaceutical sciences. 104(6):1929-1937 |
| ISSN: | 0022-3549 |
| Popis: | Development of high-concentration antibody formulations for subcutaneous administration remains challenging. Recently, a precipitation-redissolution method was proposed to prepare suspensions or precipitates of salt-dissociable protein-poly(amino acid) complexes. To elucidate the utility of this method for protein therapy, we investigated the feasibility of a precipitation-redissolution method using poly(amino acid) for high-concentration antibody formulation. Omalizumab and adalimumab formulations of 150 mg/mL could be prepared using poly-l-glutamic acid (polyE) from low-concentration stock solutions. Enzyme-linked immunosorbent assay, circular dichroism, and size-exclusion chromatography revealed that the formation of antibody-polyE complex and precipitation-redissolution process did not significantly affect the immunoreactivity or secondary structure of the antibodies. The precipitation-redissolution method was less time-consuming and more effective than lyophilization-redissolution, evaporation-redissolution, and ultrafiltration from the viewpoint of final yield. Scalability was confirmed from 400 μL to 1.0 L. The general toxicity and pharmacokinetic profiles of the antibody-polyE complex formulations were similar to those of conventional antibody formulations. These results suggested that the precipitation-redissolution method using poly(amino acid) has great potential as a concentration method for antibody formulation and medicinal use. |
| Databáze: | OpenAIRE |
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