期刊
JOURNAL OF CONTROLLED RELEASE
卷 165, 期 1, 页码 38-43出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.10.022
关键词
Stimulus-sensing material; Hyperornithinemia; Ornithine aminotransferase; Ornithine decarboxylase; Stimulus-responsive hydrogel
资金
- European Research Council under the European Community's Seventh Framework Programme/ERC [259043-CompBioMat]
- Excellence Initiative of the German Federal Government [EXC 294]
- Excellence Initiative of the German State Government [EXC 294]
Hydrogels provide a highly favorable matrix for immobilizing growth factors, enzymes or cells for biomedical applications like tissue engineering, drug delivery or the treatment of metabolic diseases. In this study we describe the synthesis and characterization of a hydrogel able to degrade L-ornithine, a metabolite that is highly elevated in congenital hyperornithinemia. The hydrogel was synthesized by embedding the L-ornithine-degrading enzymes L-ornithine aminotransferase (OAT) and L-ornithine decarboxylase (ODC) into a polymer network. The network was formed from linear polyacrylamide crosslinked by heterodimers of ODC and ornithine decarboxylase antizyme (OAz). The resulting hydrogel was shown to be stable under physiological conditions and to efficiently degrade L-ornithine. The hydrogel-stabilizing ODC-OAz interactions could subsequently be dissociated by the addition of antizyme inhibitor (AzI) which resulted in the inducible dissolution of the hydrogel. This L-ornithine-degrading hydrogel that can efficiently be eliminated when its functionality is no longer required might represent a first step towards an enzyme substitution approach against hyperornithinemia. (C) 2012 Elsevier B.V. All rights reserved.
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