Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions
The problem of gelation of concentrated protein solutions, which poses challenges for both downstream protein processing and liquid formulations of pharmaceutical proteins, is addressed herein by employing previously discovered viscosity-lowering bulky salts. Procainamide-HCl and the salt of camphor...
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| Format: | Article |
| Language: | English |
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Springer US
2018
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| Online Access: | http://hdl.handle.net/1721.1/114442 https://orcid.org/0000-0002-2639-8796 https://orcid.org/0000-0003-3830-714X |
| _version_ | 1811086624805617664 |
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| author | Awanish Kumar, Fnu Klibanov, Alexander M |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Awanish Kumar, Fnu Klibanov, Alexander M |
| author_sort | Awanish Kumar, Fnu |
| collection | MIT |
| description | The problem of gelation of concentrated protein solutions, which poses challenges for both downstream protein processing and liquid formulations of pharmaceutical proteins, is addressed herein by employing previously discovered viscosity-lowering bulky salts. Procainamide-HCl and the salt of camphor-10-sulfonic acid with l-arginine (CSA-Arg) greatly retard gelation upon heating and subsequent cooling of the model proteins gelatin and casein in water: Whereas in the absence of additives the proteins form aqueous gels within several hours at room temperature, procainamide-HCl for both proteins and also CSA-Arg for casein prevent gel formation for months under the same conditions. The inhibition of gelation by CSA-Arg stems exclusively from the CSA moiety: CSA-Na was as effective as CSA-Arg, while Arg-HCl was marginally or not effective. The tested bulky salts did not inhibit (and indeed accelerated) temperature-induced gel formation in aqueous solutions of all examined carbohydrates―starch, agarose, alginate, gellan gum, and carrageenan. Keywords: Carbohydrates, Downstream processing of biologics, Gel formation, Hydrophobic salts, Intermolecular interactions in solution, Proteins |
| first_indexed | 2024-09-23T13:29:13Z |
| format | Article |
| id | mit-1721.1/114442 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:29:13Z |
| publishDate | 2018 |
| publisher | Springer US |
| record_format | dspace |
| spelling | mit-1721.1/1144422022-09-28T14:33:57Z Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions Awanish Kumar, Fnu Klibanov, Alexander M Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Awanish Kumar, Fnu Klibanov, Alexander M The problem of gelation of concentrated protein solutions, which poses challenges for both downstream protein processing and liquid formulations of pharmaceutical proteins, is addressed herein by employing previously discovered viscosity-lowering bulky salts. Procainamide-HCl and the salt of camphor-10-sulfonic acid with l-arginine (CSA-Arg) greatly retard gelation upon heating and subsequent cooling of the model proteins gelatin and casein in water: Whereas in the absence of additives the proteins form aqueous gels within several hours at room temperature, procainamide-HCl for both proteins and also CSA-Arg for casein prevent gel formation for months under the same conditions. The inhibition of gelation by CSA-Arg stems exclusively from the CSA moiety: CSA-Na was as effective as CSA-Arg, while Arg-HCl was marginally or not effective. The tested bulky salts did not inhibit (and indeed accelerated) temperature-induced gel formation in aqueous solutions of all examined carbohydrates―starch, agarose, alginate, gellan gum, and carrageenan. Keywords: Carbohydrates, Downstream processing of biologics, Gel formation, Hydrophobic salts, Intermolecular interactions in solution, Proteins 2018-03-29T15:20:25Z 2018-03-29T15:20:25Z 2017-01 2017-07-30T03:17:11Z Article http://purl.org/eprint/type/JournalArticle 0273-2289 1559-0291 http://hdl.handle.net/1721.1/114442 Kumar, Awanish, and Alexander M. Klibanov. “Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions.” Applied Biochemistry and Biotechnology, vol. 182, no. 4, Aug. 2017, pp. 1491–96. https://orcid.org/0000-0002-2639-8796 https://orcid.org/0000-0003-3830-714X en http://dx.doi.org/10.1007/s12010-017-2413-8 Applied Biochemistry and Biotechnology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ Springer Science+Business Media New York application/pdf Springer US Springer US |
| spellingShingle | Awanish Kumar, Fnu Klibanov, Alexander M Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title | Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title_full | Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title_fullStr | Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title_full_unstemmed | Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title_short | Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions |
| title_sort | viscosity reducing bulky salt excipients prevent gelation of protein but not carbohydrate solutions |
| url | http://hdl.handle.net/1721.1/114442 https://orcid.org/0000-0002-2639-8796 https://orcid.org/0000-0003-3830-714X |
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