Agitation-induced aggregation and subvisible particulate formation in model proteins
[Display omitted] The kinetics of agitation-induced subvisible particle formation was investigated for a few model proteins – human serum albumin (HSA), hen egg white lysozyme (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the first time under relatively low protein conce...
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| Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2014-07, Vol.87 (2), p.299-309 |
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| container_title | European journal of pharmaceutics and biopharmaceutics |
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| creator | Jayaraman, Murali Buck, Patrick M. Alphonse Ignatius, Arun King, Kevin R. Wang, Wei |
| description | [Display omitted]
The kinetics of agitation-induced subvisible particle formation was investigated for a few model proteins – human serum albumin (HSA), hen egg white lysozyme (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the first time under relatively low protein concentration and low agitation speed to investigate the details of subvisible particle formation at the initial phase of aggregation ( |
| doi_str_mv | 10.1016/j.ejpb.2014.01.004 |
| format | Article |
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The kinetics of agitation-induced subvisible particle formation was investigated for a few model proteins – human serum albumin (HSA), hen egg white lysozyme (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the first time under relatively low protein concentration and low agitation speed to investigate the details of subvisible particle formation at the initial phase of aggregation (<2%) process. Upon agitation, both soluble higher molecular mass species (HMMS) and subvisible particles (SbVPs) formed at different rates, and via different mechanisms. Agitation enhanced exposure of hydrophobic sites in HSA but did not cause detectable structural changes in HEWL and IgG2. SbVPs from HSA partially dissociates in a neutral pH buffer (SEC mobile phase) but does not upon dilution in the same formulation buffer. Opposite results were obtained for SbVPs from IgG2 and HEWL. Neither the relative hydrophobic surface area nor the Tm of the model proteins seems to be an indicator of tendency for agitation-mediated SbVP formation. Taken together, our data suggests that agitation-induced SbVP formation can occur through different mechanisms and can vary, depending on the protein and solution conditions.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2014.01.004</identifier><identifier>PMID: 24462794</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aggregation ; Agitation ; Animals ; Antibodies, Monoclonal - chemistry ; Chickens ; Hot Temperature ; Humans ; Hydrogen-Ion Concentration ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin G - chemistry ; Kinetics ; Molecular Weight ; Muramidase - chemistry ; Particle ; Particle Size ; Protein ; Protein Conformation ; Protein Stability ; Serum Albumin - chemistry ; Serum Albumin, Human ; Solubility ; Stability ; Surface Properties ; Unfolding</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2014-07, Vol.87 (2), p.299-309</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-c8a9b36c07b30e6285a52474f8b95215a0b836414407da6a250ba7378c999a683</citedby><cites>FETCH-LOGICAL-c422t-c8a9b36c07b30e6285a52474f8b95215a0b836414407da6a250ba7378c999a683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0939641114000058$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24462794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jayaraman, Murali</creatorcontrib><creatorcontrib>Buck, Patrick M.</creatorcontrib><creatorcontrib>Alphonse Ignatius, Arun</creatorcontrib><creatorcontrib>King, Kevin R.</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><title>Agitation-induced aggregation and subvisible particulate formation in model proteins</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>Eur J Pharm Biopharm</addtitle><description>[Display omitted]
The kinetics of agitation-induced subvisible particle formation was investigated for a few model proteins – human serum albumin (HSA), hen egg white lysozyme (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the first time under relatively low protein concentration and low agitation speed to investigate the details of subvisible particle formation at the initial phase of aggregation (<2%) process. Upon agitation, both soluble higher molecular mass species (HMMS) and subvisible particles (SbVPs) formed at different rates, and via different mechanisms. Agitation enhanced exposure of hydrophobic sites in HSA but did not cause detectable structural changes in HEWL and IgG2. SbVPs from HSA partially dissociates in a neutral pH buffer (SEC mobile phase) but does not upon dilution in the same formulation buffer. Opposite results were obtained for SbVPs from IgG2 and HEWL. Neither the relative hydrophobic surface area nor the Tm of the model proteins seems to be an indicator of tendency for agitation-mediated SbVP formation. Taken together, our data suggests that agitation-induced SbVP formation can occur through different mechanisms and can vary, depending on the protein and solution conditions.</description><subject>Aggregation</subject><subject>Agitation</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Chickens</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Immunoglobulin G - chemistry</subject><subject>Kinetics</subject><subject>Molecular Weight</subject><subject>Muramidase - chemistry</subject><subject>Particle</subject><subject>Particle Size</subject><subject>Protein</subject><subject>Protein Conformation</subject><subject>Protein Stability</subject><subject>Serum Albumin - chemistry</subject><subject>Serum Albumin, Human</subject><subject>Solubility</subject><subject>Stability</subject><subject>Surface Properties</subject><subject>Unfolding</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMo7rr6BzxIj15a89W0BS_L4hcseFnPIUmnJaUfa9Iu-O_N2tWjp4HhmXdmHoRuCU4IJuKhSaDZ64RiwhNMEoz5GVqSPGMx45ycoyUuWBELTsgCXXnf4EBkaX6JFpRzQbOCL9FuXdtRjXboY9uXk4EyUnXtoP7pRaovIz_pg_VWtxDtlRutmVo1QlQNrpsh20fdUEIb7d0wgu39NbqoVOvh5lRX6OP5abd5jbfvL2-b9TY2nNIxNrkqNBMGZ5phEDRPVUp5xqtcFyklqcI6Z-F8znFWKqFoirXKWJaboiiUyNkK3c-5YfHnBH6UnfUG2lb1MExekpSlgmERlKwQnVHjBu8dVHLvbKfclyRYHm3KRh5tyqNNiYkMrsLQ3Sl_0h2UfyO_-gLwOAMQvjxYcNIbC32waB2YUZaD_S__Gyjxhdw</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Jayaraman, Murali</creator><creator>Buck, Patrick M.</creator><creator>Alphonse Ignatius, Arun</creator><creator>King, Kevin R.</creator><creator>Wang, Wei</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140701</creationdate><title>Agitation-induced aggregation and subvisible particulate formation in model proteins</title><author>Jayaraman, Murali ; Buck, Patrick M. ; Alphonse Ignatius, Arun ; King, Kevin R. ; Wang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-c8a9b36c07b30e6285a52474f8b95215a0b836414407da6a250ba7378c999a683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aggregation</topic><topic>Agitation</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Chickens</topic><topic>Hot Temperature</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Immunoglobulin G - chemistry</topic><topic>Kinetics</topic><topic>Molecular Weight</topic><topic>Muramidase - chemistry</topic><topic>Particle</topic><topic>Particle Size</topic><topic>Protein</topic><topic>Protein Conformation</topic><topic>Protein Stability</topic><topic>Serum Albumin - chemistry</topic><topic>Serum Albumin, Human</topic><topic>Solubility</topic><topic>Stability</topic><topic>Surface Properties</topic><topic>Unfolding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jayaraman, Murali</creatorcontrib><creatorcontrib>Buck, Patrick M.</creatorcontrib><creatorcontrib>Alphonse Ignatius, Arun</creatorcontrib><creatorcontrib>King, Kevin R.</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jayaraman, Murali</au><au>Buck, Patrick M.</au><au>Alphonse Ignatius, Arun</au><au>King, Kevin R.</au><au>Wang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Agitation-induced aggregation and subvisible particulate formation in model proteins</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>87</volume><issue>2</issue><spage>299</spage><epage>309</epage><pages>299-309</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>[Display omitted]
The kinetics of agitation-induced subvisible particle formation was investigated for a few model proteins – human serum albumin (HSA), hen egg white lysozyme (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the first time under relatively low protein concentration and low agitation speed to investigate the details of subvisible particle formation at the initial phase of aggregation (<2%) process. Upon agitation, both soluble higher molecular mass species (HMMS) and subvisible particles (SbVPs) formed at different rates, and via different mechanisms. Agitation enhanced exposure of hydrophobic sites in HSA but did not cause detectable structural changes in HEWL and IgG2. SbVPs from HSA partially dissociates in a neutral pH buffer (SEC mobile phase) but does not upon dilution in the same formulation buffer. Opposite results were obtained for SbVPs from IgG2 and HEWL. Neither the relative hydrophobic surface area nor the Tm of the model proteins seems to be an indicator of tendency for agitation-mediated SbVP formation. Taken together, our data suggests that agitation-induced SbVP formation can occur through different mechanisms and can vary, depending on the protein and solution conditions.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24462794</pmid><doi>10.1016/j.ejpb.2014.01.004</doi><tpages>11</tpages></addata></record> |
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| ispartof | European journal of pharmaceutics and biopharmaceutics, 2014-07, Vol.87 (2), p.299-309 |
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| subjects | Aggregation Agitation Animals Antibodies, Monoclonal - chemistry Chickens Hot Temperature Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Immunoglobulin G - chemistry Kinetics Molecular Weight Muramidase - chemistry Particle Particle Size Protein Protein Conformation Protein Stability Serum Albumin - chemistry Serum Albumin, Human Solubility Stability Surface Properties Unfolding |
| title | Agitation-induced aggregation and subvisible particulate formation in model proteins |
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