Supramolecular hosts as in vivo sequestration agents for pharmaceuticals and toxins

Pharmaceutical agents, drugs of abuse, and toxic substances have a large impact, positive and negative, on modern society. Efforts to mitigate the side effects of pharmaceuticals and counteract the life threatening effects of drugs of abuse and toxins can occur either by pharmacodynamic (PD) approaches based on bioreceptor·drug antagonism or by pharmacokinetic (PK) approaches that seek to reduce the concentration of free drug. In this tutorial review, we present the use of supramolecular hosts (cyclodextrins, calixarenes, (acyclic) cucurbiturils, and pillararenes) as in vivo sequestration agents for neuromuscular blockers, drugs of abuse (methamphetamine and fentanyl), anesthetics, neurotoxins, the pesticide paraquat, and heparin anti-coagulants by the PK approach. The review presents the basic physical and molecular recognition features of the supramolecular hosts and some of the principles used in their selection and structural optimization for in vivo sequestration applications. The influence of host·guest complexation on other relevant in vivo properties of drugs (e.g. distribution, circulation time, excretion, redox properties) is also mentioned. The article concludes with a discussion of future directions.