Glutathione responsive polymers and their application in drug delivery systems

Materials which respond to biological cues are the subject of intense research interest due to their possible application in smart drug delivery vehicles. In particular, novel polymers which respond to biochemical differences between the extra-and intracellular environments may be useful for preparing particles which can chaperone a therapeutic agent in the extracellular environment, and release said agent only when the particle is internalised by a target cell. To that end, polymers that exploit the elevated glutathione (GSH) concentration in the intracellular compartment are attracting substantial research effort. In this review we describe a number of different strategies for the preparation of glutathione responsive materials. In particular, we examine the use of GSH responsive linkers to prepare polymers that degrade upon exposure to millimolar concentrations of GSH, and the use of these polymers to prepare particles that disassemble at these concentrations. We also describe the use of such GSH responsive polymers in the controlled delivery of both chemotherapeutic agents and genetic material, and highlight a number of strategies employed to trigger release of an encapsulated drug using GSH. Additionally, we highlight some of the more novel GSH responsive systems which have recently been reported, and suggest further areas where GSH responsive materials are likely to see continued and highly focused research effort.