Applications of π-π stacking interactions in the design of drug-delivery systems

Abstract Noncovalent forces are of considerable importance in the formation of self-assembled drug-delivery systems. In addition to non-destructively linking the delivery vehicle and guest drug, they provide multiple advantages, including protecting the structure of the drug, maintaining its functional effects, and facilitating its release. In particular, π-π stacking interactions have potential application in a comprehensive range of biomedical and biotechnological fields. Because they do not alter structural or functional properties of drugs, π-π stacking interactions have been used as a driving force in loading drugs into delivery systems, and in the design of self-assembling systems. Moreover, since the π-π stacking force is affected by environmental conditions such as pH, it has been used to design environment-responsive drug-delivery systems. In this review, we cover features of π-π stacking interactions and their applications to the design of drug-delivery systems. Carbon nanotubes, graphene-based nanomaterials, micelles and hydrogels-all delivery systems capable of π-π stacking interactions-are the focus. We also cover π-π stacking interaction-based loading of chemicals or biological drugs into delivery systems, and controlled release of drugs from delivery systems in certain environments. In addition, we examine the in vivo barriers for π-π stacking interaction-based drug delivery, and discuss challenges for clinical applications and future directions.