title: Investigation of the complexation of albendazole with cyclodextrins for the design of new antiparasitic formulations.
abstract: Albendazole (ABZ) exhibits a potent antiparasitic activity against a broad spectrum of parasites. Unfortunately, the very low water solubility of ABZ (0.2 μg mL(-1), 0.7 μM) impairs considerably its formulation. Phase solubility diagrams showed that α-cyclodextrin (10% w/w), hydroxypropyl-β-cyclodextrin (40% w/w) and sulfobutylether-β-cyclodextrin (40% w/w) allowed an increase of apparent solubility with enhancement factors of 570, 3970, and 5880, respectively. The apparent aqueous solubility of ABZ was markedly increased from 0.2 μg mL(-1) (0.7 μM) without cyclodextrins to 1.52 mg mL(-1) (5.69 mM) with random methyl-β-cyclodextrin (Me-β-CD) (40% w/w). This corresponds to an apparent solubility enhancement factor of 7600 which is the maximal enhancement factor of ABZ apparent aqueous solubility ever reported in the literature using conventional cyclodextrins. The complexation mechanism between ABZ and cyclodextrins has been investigated using phase solubility diagrams, nuclear magnetic resonance ((1)H NMR) coupled with two-dimensional nuclear Overhauser effect (NOESY) experiments and molecular docking calculations. The results showed that the central bicyclic fragment from ABZ interacts with Me-β-CD according to 1:1 stoichiometry.
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296 Châtenay-Malabry cedex, France; BioCis, Biomolécules: conception, isolement, synthèse-Chimiothérapie Antiparasitaire, UMR CNRS 8076, Université Paris-Sud, Faculté de Pharmacie, 5, rue J.B. Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Pradines
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Centre de Recherche de Gif-sur-Yvette, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gallard
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Centre de Recherche de Gif-sur-Yvette, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Gueutin
authors.affiliation: BioCis, Biomolécules: conception, isolement, synthèse-Chimiothérapie Antiparasitaire, UMR CNRS 8076, Université Paris-Sud, Faculté de Pharmacie, 5, rue J.B. Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponchel
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296 Châtenay-Malabry cedex, France. Electronic address: kawthar.bouchemal@u-psud.fr.
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
mesh_terms: D015766:Albendazole / Q000737:chemistry*; D000977:Antiparasitic Agents / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D008958:Models, Molecular; D012995:Solubility; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000977:Antiparasitic Agents; D047392:beta-Cyclodextrins; D014867:Water; D015766:Albendazole; C031215:betadex
keywords: Albendazole; Bidimensional (1)H RMN; Cyclodextrins; Molecular docking; Solubilization studies