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  • Review Article
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Cyclodextrin-based pharmaceutics: past, present and future

Nature Reviews Drug Discovery volume 3, pages 1023–1035 (2004)Cite this article

Key Points

  • Cyclodextrins are cyclic oligomers of glucose that have a significant number of applications in the pharmaceutical industries.

  • Water-soluble cyclodextrins can form inclusion complexes with small molecules and portions of large compounds that have limited aqueous solubility to provide improved bioavailability of drugs.

  • Here, we outline the structures and properties of the most relevant cyclodextrins for pharmaceutical applications, review the history of cyclodextrin use and describe several possibilities for future applications, review the history of cyclodextrin-containing polymers and end with a discussion on the use of cyclodextrin-containing materials for gene delivery.

  • Cyclodextrins and materials containing cyclodextrins are likely to find increasing usage in a growing diversity of pharmaceutical application, most notably those involving macromolecular therapeutics.

Abstract

Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed. Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids.

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Figure 1: Schematic representations of β-cyclodextrin.
Figure 2: Schematic representations of cyclodextrins.
Figure 3: Schematic illustration of the association of free cyclodextrin (CD) and drug to form drug–CD complexes.
Figure 4: Biopharmaceutical Classification System (BCS) characterization of drugs based on solubility and permeability measures.
Figure 5
Figure 6
Figure 7: Examples of linear β-cyclodextrin-containing polymers and their use in compositions with small-molecule (top pathway) and nucleic-acid (bottom pathway) therapeutics.

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Authors and Affiliations

  1. Chemical Engineering, California Institute of Technology, Pasadena, 91125, California, USA

    Mark E. Davis

  2. Johnson & Johnson Pharmaceutical Research and Development, Turnhousteweg 30, Beerse, 2340, Belgium

    Marcus E. Brewster

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  1. Mark E. Davis
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Correspondence to Mark E. Davis.

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M.E.D. is a consultant to, and has financial interests in, Insert Therapeutics, Inc.

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DATABASES

Entrez Gene

Phosphodiesterase-5

OMIM

Buerger's disease

osteoarthritis

rheumatoid arthritis

Glossary

α-1,4- AND α-1,6- GLYCOSIDIC LINKAGES

The D-glucopyranoside unit contains six carbons and two of these units can be chemically linked from the 1-carbon of a unit to either the 4-carbon or the 6-carbon of the second unit.

HYDROPHOBIC

An affinity for, and propensity to dissolve in, non-polar solvents such as hydrocarbons.

HYDROPHILIC

An affinity for, and propensity to dissolve in, water and other polar solvents.

WETTABILITY

The wettability of a liquid is defined as the contact angle between a droplet of the liquid in thermal equilibrium on a horizontal surface.

LOG P

The logarithm of the partition coefficient of a substance in octanol–water.

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Davis, M., Brewster, M. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov 3, 1023–1035 (2004). https://doi.org/10.1038/nrd1576

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