Preparation, physicochemical characterization and biological activity evaluation of some inclusion complexes containing artesunate

Abstract

The use of cyclodextrins as carrier molecules is currently highly researched since they can improve not only the apparent water solubility and bioavailability of lipophilic drugs, but can also enhance stability or mask unpleasant tastes and smells. Artesunate is a naturally originated sesquiterpene derivative with great potential as an anticancer agent but poor water solubility. The aim of the present paper was the preparation, physicochemical characterization and biological activity assessment of three supramolecular adducts, namely guest–host inclusion complexes containing ATS as a guest molecule and randomly methylated-β-cyclodextrin (CD1), heptakis (2,6-di-O-methyl)-β-cyclodextrin (CD2) and heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (CD3), each of them used separately as hosts. The pure precursors and prepared complexes were analyzed using FTIR spectroscopy and thermal analysis, the formation of the adducts was simulated using molecular modeling and the MTT in vitro proliferation method was employed in order to evaluate their cytotoxicity on healthy (HaCaT) and pathologic (A375) skin cell lines. The instrumental techniques proved the results obtained from the molecular simulation and confirmed the formation of all three inclusion complexes. The biological activity evaluation revealed a dose-dependent cytotoxicity of ATS on the cancer cell line, effect that was diminished after complexation, but also a significantly reduced toxic effect on the healthy cells for the complexes when compared to that determined by pure ATS.