| Plain and mono-pegylated recombinant human insulin exhibit similar stress-induced aggregation profiles. | |
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MedLine Citation:
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PMID: 21344414 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PEGylation has been suggested to improve the stability of insulin, but evidence for that is scarce. Here, we compared the forced aggregation behavior of insulin and mono-PEGylated insulin. Therefore, recombinant human insulin was conjugated on lysine B29 with 5-kDa PEG. PEG-insulin was purified by size-exclusion chromatography (SEC) and characterized by mass spectrometry (MS). Next, insulin and PEG-insulin were subjected to heating at 75°C, metal-catalyzed oxidation, and glutaraldehyde cross-linking. The products were characterized physicochemically by complementary analytical methods. Mono-PEGylation of insulin was confirmed by SEC and MS. Under each of the applied stress conditions, insulin and PEG-insulin showed comparable degradation profiles. All the stressed samples showed submicron aggregates in the size range between 50 and 500 nm. Covalent aggregates and conformational changes were found for both oxidized products. Insulin and its PEGylated counterpart also exhibited similar characteristics when exposed to heat stress, that is, slightly changed secondary and tertiary structures, covalent aggregates with partially intact epitopes, and separation of chain A from chain B. Both glutaraldehyde-treated insulin and PEG-insulin contained covalent and noncovalent aggregates with intact epitopes, showed partially perturbed secondary structure, and substantial loss of tertiary structure. From these results, we conclude that PEGylation does not protect insulin against forced aggregation. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci. |
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Authors:
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Riccardo Torosantucci; Basak Kukrer; Anna Mero; Margot Van Winsen; Ruedeeporn Tantipolphan; Wim Jiskoot |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-22 |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: - ISSN: 1520-6017 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden 2300 RA, the Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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