Artemisinin extracted from Artemisia annua L.
proved to be currently, with its derivatives, the most effective
drugs against simple and severe malaria, and is also effective
on the chloroquine-resistant forms. The advantageous effect
of some cyclodextrins (CDs) on artemisinin solubilization
was demonstrated by different authors. The present work
aims to confirm the effect of several CDs on artemisinin
solubilization and to analyse the complexes formed between
these CDs and artemisinin in order to understand their
solubilization capacities. In this context, solubility studies,
liquid-state NMR spectroscopy (1H NMR studies and
ROESY experiments) as well as theoretical studies (molecular
modeling) have been performed. Randomly methylatedbCD,
Crysmeb and hydroxypropylated-cCD were also
found to improve the aqueous solubilization of artemisinin as
well as bCD, cCD and hydroxypropylated-bCD whose
effects were already demonstrated. The best solubilization
ability was found with Crysmeb. The spectroscopic studies
showed a lot of interactions between artemisinin and all the
CDs studied, but mainly outside the cavity. Molecular
modeling confirmed that artemisinin and CDs formed noninclusion
complexes.

Artemisinin,  Cyclodextrins, Non-inclusion complexes,  Solubilization, Molecular modeling