Redox-responsive minimized fragmentation of three-armed oligo(ethylene glycol) gels for protein release

Abstract

Redox-responsive drug delivery system (DDS) carriers cross-linked by disulfide bonds have attracted attention, because disulfide bonds can be cleaved in the presence of high glutathione (GSH) concentrations found in cancer cells. In this study, to obtain redox-responsive degradable hydrogels, three-armed oligo(ethylene glycol) (trisOEG) gels were prepared through terminal cross-linking reaction that linked together low-molecular-weight trisOEG molecules via a disulfide bond. The stability of the trisOEG gels was investigated in the presence of a reductant, dithiothreitol (DTT) or reduced GSH, in phosphate buffered saline solution. TrisOEG gels were fragmented by a redox-stimulus, returning the decomposed hydrophilic oligomers to a low-molecular-weight state, similar to the raw material that would be expected to be excreted in vivo by the renal system. In addition, protein-immobilized trisOEG micro-gels were prepared. While no release of entrapped protein from trisOEG micro-gel was observed in the absence of GSH, release of entrapped protein was observed in the presence of GSH at a concentration found in cytoplasm.