Monovinyl sulfone β-cyclodextrin. A flexible drug carrier system.

TitleMonovinyl sulfone β-cyclodextrin. A flexible drug carrier system.
Publication TypeJournal Article
Year of Publication2014
AuthorsDel Castillo, T., J. Marales-Sanfrutos, F. Santoyo-González, S. Magez, J. F Lopez-Jaramillo, and J. A. Garcia-Salcedo
JournalChemMedChem
Volume9
Issue2
Pagination383-9
Date Published2014 Feb
ISSN1860-7187
KeywordsAntibodies, Immobilized, beta-Cyclodextrins, Drug Carriers, Drug Delivery Systems, Humans, Nitrofurazone, Sulfones, Trypanocidal Agents, Trypanosoma brucei brucei, Trypanosomiasis, African
Abstract

Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1)a modular design that decouples the carrier function from the targeting function leads to a flexible system, 2) combining the reactivity of the vinyl sulfone group toward biomolecules that act as targeting agents with the ability of cyclodextrin to form complexes with a wide range of drugs may yield a versatile system that allows the targeting of different organs with different drugs, and 3) the higher reactivity of histidine residues toward the vinyl sulfone group can be exploited to couple the cyclodextrin to the targeting system with a degree of regioselectivity. As a proof of concept, we synthesized a monovinyl sulfone β-cyclodextrin (module responsible for the payload), which, after coupling to recombinant antibody fragments raised against Trypanosoma brucei (module responsible for targeting) and loading with nitrofurazone (module responsible for therapeutic action) resulted in an effective delivery system that targets the surface of the parasites and shows trypanocidal activity.

DOI10.1002/cmdc.201300385
Alternate JournalChemMedChem
PubMed ID24339407
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