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

Acta Biomaterialia
Hila Epstein-BarashDaniel S Kohane

Abstract

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.

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Citations

Jun 21, 2014·Chemical Society Reviews·Rong TongJianjun Cheng
Nov 8, 2013·Expert Review of Medical Devices·Axel T NeffeAndreas Lendlein
Jan 6, 2015·Macromolecular Bioscience·Ghulam JalaniMarta Cerruti
Nov 15, 2012·Clinical Therapeutics·Brian P Timko, Daniel S Kohane
Aug 26, 2014·Journal of Biomaterials Science. Polymer Edition·Eman H NafeaPenny J Martens
Mar 27, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Yitong LiYong Sun
Nov 15, 2017·Journal of Biomaterials Science. Polymer Edition·Ik Sung Cho, Tooru Ooya
Mar 13, 2020·Frontiers in Chemistry·Shaoping LuQiang Chen
Jul 14, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jin Seon KwonMoon Suk Kim
Jun 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Hansen YuXingyuan Zhang
Aug 21, 2018·Bioconjugate Chemistry·Florian A FormicaMarcy Zenobi-Wong

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