Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?
Niemann–Pick type C disease
atherosclerosis
cholesterol extraction
cyclodextrin
direct protein action
inclusion complex
ion channels
neurodegenerative diseases
non-covalent interaction
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
22 Nov 2022
22 Nov 2022
Historique:
received:
29
10
2022
revised:
15
11
2022
accepted:
18
11
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Cyclodextrins, representing a versatile family of cyclic oligosaccharides, have extensive pharmaceutical applications due to their unique truncated cone-shaped structure with a hydrophilic outer surface and a hydrophobic cavity, which enables them to form non-covalent host-guest inclusion complexes in pharmaceutical formulations to enhance the solubility, stability and bioavailability of numerous drug molecules. As a result, cyclodextrins are mostly considered as inert carriers during their medical application, while their ability to interact not only with small molecules but also with lipids and proteins is largely neglected. By forming inclusion complexes with cholesterol, cyclodextrins deplete cholesterol from cellular membranes and thereby influence protein function indirectly through alterations in biophysical properties and lateral heterogeneity of bilayers. In this review, we summarize the general chemical principles of direct cyclodextrin-protein interactions and highlight, through relevant examples, how these interactions can modify protein functions in vivo, which, despite their huge potential, have been completely unexploited in therapy so far. Finally, we give a brief overview of disorders such as Niemann-Pick type C disease, atherosclerosis, Alzheimer's and Parkinson's disease, in which cyclodextrins already have or could have the potential to be active therapeutic agents due to their cholesterol-complexing or direct protein-targeting properties.
Identifiants
pubmed: 36559052
pii: pharmaceutics14122559
doi: 10.3390/pharmaceutics14122559
pmc: PMC9788615
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : National Research, Development and Innovation Office, Hungary
ID : FK143400
Organisme : National Research, Development and Innovation Office, Hungary
ID : ANN133421
Organisme : National Research, Development and Innovation Office, Hungary
ID : K138075
Organisme : National Research, Development and Innovation Office, Hungary
ID : K143071
Organisme : National Research, Development and Innovation Office, Hungary
ID : K132906
Organisme : New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund
ID : UNKP-22-4-II-DE-69
Déclaration de conflit d'intérêts
L.S. is currently employed by the Cyclodextrin R & D Laboratory Ltd. The remaining authors declare no conflict of interest. The funders had no role in the writing of the manuscript.
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