An in situ cross-linking hybrid hydrogel for controlled release of proteins.

An in situ cross-linking hybrid hydrogel for controlled release of proteins.
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DOI:
10.1016/j.actbio.2012.01.028
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发表时间:
2012-05
期刊:
影响因子:
9.7
通讯作者:
Kohane, Daniel S.
Kohane, Daniel S.
中科院分区:
工程技术1区
文献类型:
--
作者:
Epstein-Barash, Hila;Stefanescu, Cristina F.;Kohane, Daniel S.

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There is a clear need for methods of providing safe controlled release of therapeutic proteins, either to achieve and maintain high local protein concentrations, or for sustained systemic delivery. Here we have developed a protein delivery system combining in situ cross-linkable polysaccharide hydrogels with gelatin. This formulation is injectable, easy to apply, and obviates the need for organic solvents or potentially toxic cross-linking agents in the formulation process. The cross-linked polysaccharides themselves (comprising hyaluronic acid, dextran, and/or carboxymethylcellulose) provided prolonged release of fluorescently-labeled albumin (FITC-albumin). The duration of release was markedly extended by the incorporation of gelatin into the formulation: FITC-albumin and IL-2 were released over the course of more than three weeks. The IL-2 maintained > 70% activity throughout that time. Gelatin also accelerated the gelation time of the hydrogels, and reduced their swelling in phosphate buffered saline. The composite hydrogel (dextran-carboxymethylcellulose-gelatin) showed minimal cytotoxicity in vitro, and benign tissue reaction after subcutaneous injection in rats.
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