Pharmacokinetic study of intravenously administered artemisinin-loaded surface-decorated amphiphilic γ-cyclodextrin nanoparticles.

Autor: Gérard Yaméogo JB; Univ. Grenoble Alpes, CNRS, DPM, F-38000, Grenoble, France; UFR/SDS, University Ouaga I Pr Joseph Ki-Zerbo, Burkina Faso., Mazet R; Univ. Grenoble Alpes, CNRS, DPM, F-38000, Grenoble, France; Pôle Pharmacie, Grenoble University Hospital, 38000, Grenoble, France., Wouessidjewe D; Univ. Grenoble Alpes, CNRS, DPM, F-38000, Grenoble, France., Choisnard L; Univ. Grenoble Alpes, CNRS, DPM, F-38000, Grenoble, France., Godin-Ribuot D; Laboratoire HP2/U1042 INSERM, Faculty of Pharmacy, Univ. Grenoble Alpes, France., Putaux JL; Univ. Grenoble Alpes, CNRS, CERMAV, F-38000, Grenoble, France., Semdé R; UFR/SDS, University Ouaga I Pr Joseph Ki-Zerbo, Burkina Faso., Gèze A; Univ. Grenoble Alpes, CNRS, DPM, F-38000, Grenoble, France. Electronic address: annabelle.geze@univ-grenoble-alpes.fr.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2020 Jan; Vol. 106, pp. 110281. Date of Electronic Publication: 2019 Oct 07.
DOI: 10.1016/j.msec.2019.110281
Abstrakt: 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 surface-decorated nanoparticles were prepared by co-nanoprecipitation of γ-cyclodextrin bioesterified with C 10 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 (AUC 0-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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: