Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis
Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402308920X |
| _version_ | 1797429867666472960 |
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| author | Laura J. Waters Joseph Whiteley William Small Steve Mellor |
| author_facet | Laura J. Waters Joseph Whiteley William Small Steve Mellor |
| author_sort | Laura J. Waters |
| collection | DOAJ |
| description | Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In this work we propose a modified form of a recently published UV spectroscopic method that identifies protein unfolding. In this study we determine concentration limits to avoid protein unfolding of two model surfactants, namely polysorbate 20 and polysorbate 80, by correlating surfactant concentration with percentage ‘unfolded’ for three model proteins. For each scenario two distinct regions were observed, firstly surfactant concentrations at which no unfolding had occurred, followed by a second region whereby unfolding steadily increased with surfactant concentration. In general for the combinations analysed in this study, this second region began to appear around ten times below the critical micellar concentration of each surfactant, regardless of the protein or polysorbate chosen. It is therefore proposed that this adapted method could be used by researchers in the early stages of formulation development as a convenient and simple screening tool to confirm the ‘onset of unfolding’ concentration for protein-surfactant formulations, thus helping to optimise surfactant concentration selection in pharmaceutical formulations to maintain the benefits of surfactants yet avoid inadvertent unfolding. |
| first_indexed | 2024-03-09T09:19:08Z |
| format | Article |
| id | doaj.art-ae870c1aa3ba411296fee1162e5dc82b |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:19:08Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-ae870c1aa3ba411296fee1162e5dc82b2023-12-02T07:03:56ZengElsevierHeliyon2405-84402023-11-01911e21712Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysisLaura J. Waters0Joseph Whiteley1William Small2Steve Mellor3School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK; Corresponding author.School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UKCroda Europe Ltd, Cowick Hall, Snaith, Goole, DN14 9AA, UKCroda Europe Ltd, Cowick Hall, Snaith, Goole, DN14 9AA, UKProtein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In this work we propose a modified form of a recently published UV spectroscopic method that identifies protein unfolding. In this study we determine concentration limits to avoid protein unfolding of two model surfactants, namely polysorbate 20 and polysorbate 80, by correlating surfactant concentration with percentage ‘unfolded’ for three model proteins. For each scenario two distinct regions were observed, firstly surfactant concentrations at which no unfolding had occurred, followed by a second region whereby unfolding steadily increased with surfactant concentration. In general for the combinations analysed in this study, this second region began to appear around ten times below the critical micellar concentration of each surfactant, regardless of the protein or polysorbate chosen. It is therefore proposed that this adapted method could be used by researchers in the early stages of formulation development as a convenient and simple screening tool to confirm the ‘onset of unfolding’ concentration for protein-surfactant formulations, thus helping to optimise surfactant concentration selection in pharmaceutical formulations to maintain the benefits of surfactants yet avoid inadvertent unfolding.http://www.sciencedirect.com/science/article/pii/S240584402308920XBiocompatibilityCritical micellar concentrationPharmaceuticalPolysorbateProteinSpectroscopy |
| spellingShingle | Laura J. Waters Joseph Whiteley William Small Steve Mellor Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis Heliyon Biocompatibility Critical micellar concentration Pharmaceutical Polysorbate Protein Spectroscopy |
| title | Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis |
| title_full | Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis |
| title_fullStr | Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis |
| title_full_unstemmed | Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis |
| title_short | Determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using UV analysis |
| title_sort | determining suitable surfactant concentration ranges to avoid protein unfolding in pharmaceutical formulations using uv analysis |
| topic | Biocompatibility Critical micellar concentration Pharmaceutical Polysorbate Protein Spectroscopy |
| url | http://www.sciencedirect.com/science/article/pii/S240584402308920X |
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