Understanding the interactions between artemisinin and cyclodextrins: spectroscopic studies and molecular modeling

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 (H-1 NMR studies and ROESY experiments) as well as theoretical studies (molecular modeling) have been performed. Randomly methylated-beta CD, Crysmeb(A (R)) and hydroxypropylated-gamma CD were also found to improve the aqueous solubilization of artemisinin as well as beta CD, gamma CD and hydroxypropylated-beta CD whose effects were already demonstrated. The best solubilization ability was found with Crysmeb(A (R)). 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 non-inclusion complexes.