title: Monovinyl sulfone β-cyclodextrin. A flexible drug carrier system.
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.
authors: Hospital Universitario San Cecilio, Instituto de Investigaciones Biosanitarias de Granada, FIBAO, Granada (Spain); Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada (Spain).
authors: Teresa
authors: T
authors: del Castillo
authors: Julia
authors: J
authors: Marales-Sanfrutos
authors: Francisco
authors: F
authors: Santoyo-González
authors: Stefan
authors: S
authors: Magez
authors: F Javier
authors: FJ
authors: Lopez-Jaramillo
authors: Jose A
authors: JA
authors: Garcia-Salcedo
mesh_terms: D055910:Antibodies, Immobilized / Q000737:chemistry / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D009583:Nitrofurazone / Q000008:administration & dosage* / Q000494:pharmacology; D013450:Sulfones / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000276:immunology; D014353:Trypanosomiasis, African / Q000188:drug therapy; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D055910:Antibodies, Immobilized; D004337:Drug Carriers; D013450:Sulfones; D014344:Trypanocidal Agents; D047392:beta-Cyclodextrins; C009873:divinyl sulfone; C031215:betadex; D009583:Nitrofurazone
keywords: bioconjugation; cyclodextrins; drug delivery; vinyl sulfones