Enzymatic hydrolysis of diloxanide furoate in the presence of beta-cyclodextrin and its methylated derivatives.
In this study, we investigated the susceptibility to enzymatic and alkaline hydrolysis of diloxanide furoate (DF) and its cyclodextrin inclusion complexes, in aqueous solution. The cyclodextrins (CDs) utilized were beta-cyclodextrin (beta-CD), (2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) and (2,3,6-tri-O-methyl)-beta-cyclodextrin (TM-beta-CD). All cyclodextrins studied provided a stabilizing effect to diloxanide furoate hydrolysis. In alkaline hydrolysis (pH 10.75), without the enzyme, beta-CD and TM-beta-CD provided similar effect on the stability of DF, with an inhibition factor in the order of 2.0. The DM-beta-CD, on the other hand, provided more pronounced stabilization effect than the other two CDs, with an inhibition factor around of 8. The maximum activity of the enzyme occured around pH 7.0. In the presence of enzyme, all cyclodextrins produced similar effect, with a DF hydrolysis inhibition factor in the order of 10. However, the plot of rate of hydrolysis versus [CD] fit with a equation based in a model that considers the association of the enzyme with the CDs. Therefore, it is concluded that the stabilization of DF is not only due to its cyclodextrin complex but also due to enzyme inhibition by cyclodextrin complexation.
Monteiro
Julieta B
JB
Departamento de Química, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, -SC 88040-900, Florianópolis, Brazil.
Chiaradia
Louise D
LD
Brandão
Tiago A S
TA
Magro
Jacir Dal
JD
Yunes
Rosendo A
RA
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005663:Furans / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008049:Lipase / Q000494:pharmacology; D008745:Methylation / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D005663:Furans; D047392:beta-Cyclodextrins; D008049:Lipase; C031215:betadex; C004932:diloxanide furoate