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

作者：Epstein Barash Hila; Stefanescu Cristina F; Kohane Daniel S^*

来源：Acta Biomaterialia, 2012, 8(5): 1703-1709.

DOI：10.1016/j.actbio.2012.01.028

• Controlled release
• Protein
• Gelatin
• Drug delivery
• Hydrogel

There is a clear need for methods to provide a safe controlled release of therapeutic proteins, either to achieve and maintain high local protein concentrations, or for sustained systemic delivery. We have developed a protein delivery system that combines 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 interleukin-2 (IL-2) were released over the course of more than 3 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.

• 出版日期2012-5