Hammer, Nadine and Brandl, Ferdinand P. and Kirchhof, Susanne and Goepferich, Achim M. (2014) Cleavable carbamate linkers for controlled protein delivery from hydrogels. JOURNAL OF CONTROLLED RELEASE, 183. pp. 67-76. ISSN 0168-3659, 1873-4995
Full text not available from this repository. (Request a copy)Abstract
The reversible attachment of proteins to polymers is one potential strategy to control protein release from hydrogels. In this study, we report the reversible attachment of lysozyme to poly(ethylene glycol) (PEG) by degradable carbamate linkers. Phenyl groupswith different substituents were used to control the rate of carbamate hydrolysis and the resulting protein release. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed modification with 1-3 PEG chains per lysozyme molecule. Protein PEGylation and PEG chain elimination occurred without changes in secondary protein structure, as demonstrated by circular dichroism spectroscopy. The lytic activity of lysozyme was restored to 73.4 +/- 1.7%-92.5 +/- 1.2% during PEG chain elimination. Attached PEG chains were eliminated within 24 h to 28 days, depending on the used linker molecule. When formulated into hydrogels, a maximum of about 60% of the initial dose was released within 7 days to 21 days. Linker elimination occurs 'traceless', so that the protein is released in its native, unmodified form. Altogether, we believe that tethering proteins by degradable carbamate linkers is a promising strategy to control their release from hydrogels. (C) 2014 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMS EMPLOYING 1,6-ELIMINATION; DEGRADABLE POLY(ETHYLENE GLYCOL); CONTROLLED-RELEASE; DRUG-DELIVERY; TRIGGERED RELEASE; PEPTIDE ACYLATION; AMINO-ACIDS; HYDROLYSIS; PEGYLATION; IMMOBILIZATION; Poly(ethylene glycol); Hydrogel; Protein tethering; Cleavable linker; Reversible PEGylation; Release |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2019 09:07 |
| Last Modified: | 28 Oct 2019 09:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10031 |
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