Supramolecular prodrugs based on host–guest interactions

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Abstract
Classic prodrug strategies rely on covalent modification of active drugs to provide systems with superior pharmacokinetic properties than the parent drug and facilitate administration. Supramolecular chemistry is providing a new approach to developing prodrug-like systems, wherein the characteristics of a drug are modified in a beneficial manner by creating host–guest complexes that then permit the stimulus-induced release of the active species in a controlled manner. These complexes are termed “supramolecular prodrugs”. In this review, we outline the concept of supramolecular drugs via host–guest chemistry and detail progress made in the area. This summary is designed to highlight the many advantages of supramolecular prodrugs, including ease-of-preparation, molecular-level protection, sensitive response to bio-stimuli, traceless release, and adaptability to different drugs. Limitations of the approach and opportunities for future growth are also detailed.
Funding Information
  • National Natural Science Foundation of China (31961143004)
  • National Natural Science Foundation of China (51873090)
  • National Institute of General Medical Sciences (RO1 GM103790)
  • Welch Foundation (F-0018)
  • China Scholarship Council (201806200072)

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