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

• Published in: Materials Science & Engineering C 2020-01, Vol.106, p.110281, Article 110281
• Main Authors: Gérard Yaméogo, Josias Boumbéwendin, Mazet, Roseline, Wouessidjewe, Denis, Choisnard, Luc, Godin-Ribuot, Diane, Putaux, Jean-Luc, Semdé, Rasmané, Gèze, Annabelle
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Animals; Antimalarials - blood; Antimalarials - chemistry; Antimalarials - pharmacokinetics; Aqueous solutions; Artemisinin; Artemisinins - blood; Artemisinins - chemistry; Artemisinins - pharmacokinetics; Bioavailability; Bioesterified γ-cyclodextrins; Cyclodextrin; Cyclodextrins; Decoration; Derivatives; Drug Carriers - chemistry; Ethanol; Galenic pharmacology; gamma-Cyclodextrins - chemistry; Half-Life; Healthy rats; In vivo methods and tests; Intravenous administration; Life Sciences; Malaria; Male; Materials science; Nanoparticles; Nanoparticles - chemistry; Nanospheres; Particle Size; Pharmaceutical sciences; Pharmacokinetic parameters; Pharmacokinetics; Pharmacology; Polyethylene glycol; Polyethylene Glycols - chemistry; Rats; Rats, Wistar; Surface Properties; Surface-decorated nanoparticles; Vector-borne diseases
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.110281

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 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. [Display omitted] •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.•In comparison to this reference ART solution, 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.•Moreover, its plasma half-life increased by a factor of 4.00 and 6.25-fold respectively and its clearance decreased up to 2.5 and 4.72-fold.•The overall behaviour of nanoparticles is rather conducive to effective management of severe malaria.•This PK parameters improvement is significant by comparison with the literature data.