Investigation of the complexation of albendazole with cyclodextrins for the design of new antiparasitic formulations.
Carbohydr Res
; 398: 50-5, 2014 Oct 29.
Article
em En
| MEDLINE
| ID: mdl-25240182
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-ß-cyclodextrin (40% w/w) and sulfobutylether-ß-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-ß-cyclodextrin (Me-ß-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-ß-CD according to 11 stoichiometry.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Albendazol
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Beta-Ciclodextrinas
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Antiparasitários
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Carbohydr Res
Ano de publicação:
2014
Tipo de documento:
Article