دورية أكاديمية
Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques.
| العنوان: | Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques. |
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| المؤلفون: | Västberg A; Research Institutes of Sweden, Drottning Kristinas väg 61B, 11428 Stockholm, Sweden; Department of Food Technology, Engineering and Nutrition, Faculty of Engineering LTH, Lund University, Lund, Sweden. Electronic address: amanda.vastberg@ri.se., Bolinsson H; Department of Food Technology, Engineering and Nutrition, Faculty of Engineering LTH, Lund University, Lund, Sweden., Leeman M; Solve Research & Consultancy, Lund, Sweden., Nilsson L; Department of Food Technology, Engineering and Nutrition, Faculty of Engineering LTH, Lund University, Lund, Sweden., Nylander T; Physical Chemistry, Department of Chemistry, Lund University, Lund, Sweden., Sejwal K; Vironova AB, Stockholm, Sweden., Sintorn IM; Vironova AB, Stockholm, Sweden., Lidayová K; Vironova AB, Stockholm, Sweden., Sjögren H; Ferring Pharmaceuticals, Kastrup, Denmark., Wahlgren M; Department of Food Technology, Engineering and Nutrition, Faculty of Engineering LTH, Lund University, Lund, Sweden., Elofsson U; Research Institutes of Sweden, Drottning Kristinas väg 61B, 11428 Stockholm, Sweden. |
| المصدر: | International journal of pharmaceutics [Int J Pharm] 2023 Apr 25; Vol. 637, pp. 122829. Date of Electronic Publication: 2023 Mar 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| مواضيع طبية MeSH: | Human Growth Hormone*, Dynamic Light Scattering ; Calorimetry, Differential Scanning |
| مستخلص: | Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0. The techniques were Dynamic Light Scattering (DLS), Asymmetric Flow-Field Flow-Fractionation (AF4), and the TEM-based analysis system MiniTEM™. In addition, Differential Scanning Calorimetry (DSC) was used to study the thermal unfolding and stability. DSC and DLS were used to explain the initial aggregation process and aggregation rate at the two pH values. The results suggest that less electrostatic stabilization seems to be the main reason for the faster initial aggregation at pH 5.8, i.e., closer to the isoelectric point of Somatropin. AF4 and MiniTEM were used to investigate the aggregation pathway further. Combining the results allowed us to demonstrate Somatropin's thermal aggregation pathway at pH 7.0. The growth of the aggregates appears to follow two steps. Smaller elongated aggregates are formed in the first step, possibly initiated by partly unfolded species. In the second step, occurring during longer heating, the smaller aggregates assemble into larger aggregates with more complex structures. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| المشرفين على المادة: | 12629-01-5 (Human Growth Hormone) |
| تواريخ الأحداث: | Date Created: 20230322 Date Completed: 20230424 Latest Revision: 20230424 |
| رمز التحديث: | 20230424 |
| DOI: | 10.1016/j.ijpharm.2023.122829 |
| PMID: | 36948472 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-3476 |
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| DOI: | 10.1016/j.ijpharm.2023.122829 |