A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation
<b>Background/Objectives:</b> Protein aggregation, particularly the aggregation of antibody-based drugs, has long been a significant challenge in downstream processes and formulation. While the inhibitory effects of excipients on aggregation have been extensively studied using early expe...
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MDPI AG
2025-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/17/4/534 |
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| author | Yibo Guo Xi Chen Guchen Fang Xuejun Cao Junfen Wan |
| author_facet | Yibo Guo Xi Chen Guchen Fang Xuejun Cao Junfen Wan |
| author_sort | Yibo Guo |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Protein aggregation, particularly the aggregation of antibody-based drugs, has long been a significant challenge in downstream processes and formulation. While the inhibitory effects of excipients on aggregation have been extensively studied using early experimental characterization methods, complete formulation research requires significant amounts of antibodies and time, resulting in high research costs. <b>Methods:</b> This study proposed a quick and small-scale position-restrained simulation method which elucidated the mechanism of the reversible self-association (RSA) of antibodies and the influence of excipients on RSA under different conditions. We also validated the rationality of rapid and small-scale simulations through long-term (>1 μs) and large-scale (>1,000,000 atoms) simulations. <b>Results</b>: Through combing with simple stability characterization, the effects of different excipients on monomer residual content and the trend shown with concentration changes after thermal incubation were found to be similar to those observed in the simulations. Additionally, the formulation proposed by the simulations was validated using experimental characterization. <b>Conclusions</b>: Simulations and experiments revealed the mechanism and showed consistent trends, providing better understanding for aggregation research. |
| format | Article |
| id | doaj-art-d59e09abf8094f1aa94769c626e189bd |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-d59e09abf8094f1aa94769c626e189bd2025-08-20T03:13:51ZengMDPI AGPharmaceutics1999-49232025-04-0117453410.3390/pharmaceutics17040534A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and SimulationYibo Guo0Xi Chen1Guchen Fang2Xuejun Cao3Junfen Wan4State Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China<b>Background/Objectives:</b> Protein aggregation, particularly the aggregation of antibody-based drugs, has long been a significant challenge in downstream processes and formulation. While the inhibitory effects of excipients on aggregation have been extensively studied using early experimental characterization methods, complete formulation research requires significant amounts of antibodies and time, resulting in high research costs. <b>Methods:</b> This study proposed a quick and small-scale position-restrained simulation method which elucidated the mechanism of the reversible self-association (RSA) of antibodies and the influence of excipients on RSA under different conditions. We also validated the rationality of rapid and small-scale simulations through long-term (>1 μs) and large-scale (>1,000,000 atoms) simulations. <b>Results</b>: Through combing with simple stability characterization, the effects of different excipients on monomer residual content and the trend shown with concentration changes after thermal incubation were found to be similar to those observed in the simulations. Additionally, the formulation proposed by the simulations was validated using experimental characterization. <b>Conclusions</b>: Simulations and experiments revealed the mechanism and showed consistent trends, providing better understanding for aggregation research.https://www.mdpi.com/1999-4923/17/4/534protein aggregationMD simulationbispecific antibodysingle-chain fragment variable |
| spellingShingle | Yibo Guo Xi Chen Guchen Fang Xuejun Cao Junfen Wan A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation Pharmaceutics protein aggregation MD simulation bispecific antibody single-chain fragment variable |
| title | A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation |
| title_full | A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation |
| title_fullStr | A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation |
| title_full_unstemmed | A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation |
| title_short | A Convenient Strategy for Studying Antibody Aggregation and Inhibition of Aggregation: Characterization and Simulation |
| title_sort | convenient strategy for studying antibody aggregation and inhibition of aggregation characterization and simulation |
| topic | protein aggregation MD simulation bispecific antibody single-chain fragment variable |
| url | https://www.mdpi.com/1999-4923/17/4/534 |
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