Article

Projet
 
Denis WOUESSIDJEWE, Annabelle GEZE, Luc CHOISNARD,   
Titre
Pharmacokinetic study of intravenously administered artemisinin-loaded surface-decorated amphiphilic γ-cyclodextrin nanoparticles  
[Full paper ]
Auteurs
J. Boumbéwendin Gérard Yaméogo, R. Mazet, D. Wouessidjewe, L. Choisnard, D. Godin-Ribuot, J.-L. Putaux, R. Semdé, A. Gèze
Edition
Mat. Sci. Engin. C 2020, 106, 110281
Année
2020
Résumé
Artemisinin and its derivatives are currently recommended by World Health Organization for the treatment of malaria. Severe malaria requires a parenteral administration of artemisinin-based formulations. However, the effective use of artemisinin is limited by the pharmacokinetic characteristics of the drug (low water solubility, poor bioavailability and short half-life). To overcome some of these drawbacks, artemisinin-loaded surfacedecorated nanoparticles were prepared by co-nanoprecipitation of γ-cyclodextrin bioesterified with C10 alkyl chains and polyethylene glycol (PEG) derivatives (polysorbate 80 and DMPE-mPEG2000). Using a single dose (1.5 mg kg−1 or 2 mg kg−1) by intravenous administration, we investigated the in vivo pharmacokinetic properties in healthy rats of two types of artemisinin-loaded nanoparticle formulations, namely, nanosphere and nanoreservoir systems versus an ethanolic-aqueous solution of artemisinin as reference. Significantly enhanced pharmacokinetic parameters were obtained with artemisinin-loaded nanoparticles. In comparison to reference formulation, the geometric mean exposures in plasma (AUC0-t) exhibited 2.35 and 3.26-fold increases when artemisinin was loaded in nanoreservoir and nanosphere systems, respectively. Its plasma half-life increased 4.00 and 6.25-fold and its clearance decreased up to 2.5 and 4.72-fold. Artemisinin was successfully administered intravenously by means of surface-decorated amphiphilic γ-cyclodextrin nanostructures and showed a longer elimination half-life with respect to an artemisinin solution in ethanol. Therefore, these systems are likely to provide significant advantages for the intravenous treatment of severe malaria.