Artemisinin (ART), an endoperoxide sesquiterpene lactone antimalarial drug isolated from a Chinese medicinal herb (Artemisia annua), has a fast action against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, making it very effective in the treatment of multidrug-resistant malaria. However, its poor aqueous solubility, short half-life, and high first-pass metabolism limit its use in therapeutics. The purpose of the present study was to investigate the potential of self-assembled bio-transesterified CD-based nanocarriers as ART delivery systems for an intravenous route. The objective of our study was twofold: (i) to improve the ART dosage through its association with CD esters-based nanocarriers, (ii) to ensure a sufficient blood circulation time of the nanocarriers through their surface decoration, which is a prerequisite to reach infected erythrocytes after systemic administration. Stable colloidal suspensions with good ART association rate were developed to solve the problem of insolubility in aqueous medium of the active molecule and therefore consider its parenteral administration. The γ-CD-C 10 based nanospheres showed a significant sustained release profile of ART extended up to 4 days for nanosphères and 11 days for nanoreservoirs. In addition to the physicochemical characterizations, the potential of nanoparticles decorated on the surface were evaluated and compared in biological tests. The results from this study indicate that ART-loaded nanosystems, mainly PEGylated ones exhibit satisfactory in vitro activity against Chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum with very low IC50 of the order of 3 to 6 ng / mL. The concept of co-assembly of nano-amphiphilic derivatives of γ-CD-C10 bioestérifiée and polyethylene glycol (PEG) under conditions of nanoprecipitation seems to be an interesting approach to impart stealth nano-systems-γ-CD C10. Indeed, in vitro studies show a significant decrease in phagocytosis by macrophages and/or adsorption of serum complement proteins on the surface of nanoparticles of γ-CD-C10 decorated by polysorbate 80, PEG1500 stearate, and mPEG2000-DMPE. In vivo, we observed an increase in blood circulation time of nanoreservoirs γ-CD-C10/polysorbate 80 and nanospheres γ-CD-C10/DMPE-mPEG2000. Finally, pharmacokinetic studies in rats show that the pharmacokinetics of ART are enhanced when combined with previous two nanoparticle systems. Indeed, values of plasma clearance and very low time of long plasma half-life (3 to 5 hours, respectively) of ART were recorded with both formulations. These colloidal forms of ART developed open up interesting prospects for the therapeutic treatment of severe malaria.
