Melarsoprol-cyclodextrins inclusion complexes. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue International Journal of Pharmaceutics Année : 2005

Melarsoprol-cyclodextrins inclusion complexes.

Résumé

Melarsoprol, a water-insoluble drug, is mainly used in the treatment of trypanosomiasis and has demonstrated an in vitro activity on myeloid and lymphoid leukemia derived cell lines. It is marketed as a very poorly tolerated non-aqueous solution (Arsobal). The aim of our work was to develop melarsoprol-cyclodextrin complexes in order to improve the tolerability and the bioavailability of melarsoprol. Phase-solubility analysis showed A(L)-type diagrams with beta-cyclodextrin (betaCD), randomly methylated beta-cyclodextrin (RAMEbetaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD), which suggested the formation of 1:1 inclusion complexes. The solubility enhancement factor of melarsoprol (solubility in 250 mM of cyclodextrin/solubility in water) was about 7.2x10(3) with both beta-cyclodextrin derivatives. The 1:1 stoichiometry was confirmed in the aqueous solutions by the UV spectrophotometer using Job's plot method. The apparent stability constants K(1:1), calculated from mole-ratio titration plots, were 57 143+/-4 425M(-1) for RAMEbetaCD and 50 761+/-5 070 M(-1) for HPbetaCD. Data from 1H-NMR and ROESY experiments provided a clear evidence of inclusion complexation of melarsoprol with its dithiaarsane extremity inserted into the wide rim of the cyclodextrin torus. Moreover, RAMEbetaCD had a pronounced effect on the drug hydrolysis and the dissolution rate of melarsoprol. However, the cytotoxic properties of melarsoprol on K562 and U937 human leukemia cell lines was not modified by complexation.
Fichier principal
Vignette du fichier
IJP-D-05-00120.pdf (897.25 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00399630 , version 1 (06-10-2016)

Identifiants

Citer

Stéphane Gibaud, Siham Ben Zirar, Pierre Mutzenhardt, Isabelle Fries, Alain Astier. Melarsoprol-cyclodextrins inclusion complexes.. International Journal of Pharmaceutics, 2005, 306 (1-2), pp.107-21. ⟨10.1016/j.ijpharm.2005.09.003⟩. ⟨hal-00399630⟩
198 Consultations
392 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More