Disulfide chemistry in responsive aggregation of amphiphilic systems

The dynamic nature of the disulfide bond has enhanced the potential for disulfide based amphiphiles in the emerging biomedical field. Disulfide containing amphiphiles have extensively been used for constructing wide ranging soft nanostructures as potential candidates for delivery of drugs, proteins and genes owing to their degradable nature in the presence of intracellular glutathione (present in a many fold excess compared to the extracellular milieu). This degradable nature of amphiphiles is not only useful to deliver therapeutics but it also eliminates the toxicity issues associated with the carrier after delivery of such therapeutics. Therefore, these bioreducible and biocompatible nano-aggregates inspired researchers to use them as vehicles for therapeutic delivery and as a result the literature of disulfide containing amphiphiles has been intensified. This review article highlights the structural diversity in disulfide containing amphiphilic small molecule and polymeric systems, structural effects on their aqueous aggregation, redox-responsive disassembly and biological applications. Furthermore, the use of disulfide chemistry towards the design of cell penetrating polymers has also been discussed. Finally a brief perspective on some future opportunities of these systems is provided.