Abstract

The rational design of drug delivery approaches leveraging supramolecular chemistry (i.e., “chemistry beyond the molecule”) has garnered significant interest in recent years toward improving therapeutics. By using specific, dynamic, and tunable non-covalent interactions, engineered approaches to drug delivery can be realized. Certain benefits to this approach are molecular-level control of composition, improved routes for incorporating and targeting drugs, and new strategies to create delivery devices that respond to a variety of physiologic indicators. Some of the most recognizable supramolecular motifs – macrocyclic host–guest complexes – afford logical application to drug delivery in using drug as guest. The use of supramolecular motifs may further give rise to materials for the controlled encapsulation and release of therapeutics. Furthermore, given the majority of supramolecular motifs in water are directed by hydrophobic interactions, cooperative delivery strategies can be realized. The modularity of supramolecular interactions also facilitates opportunities to combine multiple drugs within one delivery platform, as well as the facile incorporation of targeting units. In sum, supramolecular design offers ample opportunity to improve the precision of pharmaceutical practice. In the context of clinical translation, features of supramolecular design may prove additionally advantageous, specifically in enabling quantitative drug loading, molecularly discrete delivery devices, and a priori knowledge of carrier degradation and clearance mechanisms. As such, the design opportunities afforded by supramolecular chemistry will play a vital role in the future of the drug delivery field.

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