Structural Characterization of IgG1 mAb Aggregates and Particles Generated under Various Stress Conditions
dc.contributor.author | Telikepalli, Srivalli | |
dc.contributor.author | Kumru, Ozan S. | |
dc.contributor.author | Kalonia, Cavan Kumar | |
dc.contributor.author | Esfandiary, Reza | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Middaugh, C. Russell | |
dc.contributor.author | Volkin, David B. | |
dc.date.accessioned | 2017-04-26T17:48:00Z | |
dc.date.available | 2017-04-26T17:48:00Z | |
dc.date.issued | 2014-03 | |
dc.identifier.citation | Telikepalli, S. N., Kumru, O. S., Kalonia, C., Esfandiary, R., Joshi, S. B., Middaugh, C. R., & Volkin, D. B. (2014). Structural Characterization of IgG1 mAb Aggregates and Particles Generated under Various Stress Conditions. Journal of Pharmaceutical Sciences, 103(3), 796–809. http://doi.org/10.1002/jps.23839 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23814 | |
dc.description.abstract | IgG1 mAb solutions were prepared with and without sodium chloride and subjected to different environmental stresses. Formation of aggregates and particles of varying size was monitored by a combination of size exclusion chromatography (SEC), Nanosight Tracking Analysis (NTA), Micro-flow Imaging (MFI), turbidity, and visual assessments. Stirring and heating induced the highest concentration of particles. In general, the presence of NaCl enhanced this effect. The morphology of the particles formed from mAb samples exposed to different stresses was analyzed from TEM and MFI images. Shaking samples without NaCl generated the most fibrillar particles, while stirring created largely spherical particles. The composition of the particles was evaluated for covalent cross-linking by SDS-PAGE, overall secondary structure by FTIR microscopy, and surface apolarity by extrinsic fluorescence spectroscopy. Freeze-thaw and shaking led to particles containing protein with native-like secondary structure. Heating and stirring produced IgG1 containing aggregates and particles with some non-native disulfide crosslinks, varying levels of intermolecular beta sheet content, and increased surface hydrophobicity. These results highlight the importance of evaluating protein particle morphology and composition, in addition to particle number and size distributions, to better understand the effect of solution conditions and environmental stresses on the formation of protein particles in mAb solutions. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Protein | en_US |
dc.subject | Aggregation | en_US |
dc.subject | Particles | en_US |
dc.subject | Formulation | en_US |
dc.subject | Monoclonal antibody | en_US |
dc.subject | IgG | en_US |
dc.subject | Accelerated stability | en_US |
dc.title | Structural Characterization of IgG1 mAb Aggregates and Particles Generated under Various Stress Conditions | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Telikepalli, Srivalli N. | |
kusw.kuauthor | Kumru, Ozan S. | |
kusw.kuauthor | Kalonia, Cavan | |
kusw.kuauthor | Esfandiary, Reza | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Middaugh, C. Russell | |
kusw.kuauthor | Volkin, David B. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1002/jps.23839 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4040128 | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.