Guest–host interactions and complex formation for artemisinin with cyclodextrins: instrumental analysis and evaluation of biological activity

Artemisinin is one of the most important naturally occurring compound found in Artemisia annua , being highly active against Plasmodium falciparum , the malaria causing parasite, and currently studied in the oncological field. The aim of this study was to obtain and characterize the host–guest inclusion complexes formed between artemisinin and three functionalized cyclodextrins, namely 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). As instrumental tools, thermal analysis (TG/DTG/HF) and UATR-FTIR spectroscopy were used. Later on, the inclusion complexes were tested as to evaluate their antioxidant (AOA) and in vitro activity on both healthy keratinocytes and a human melanoma cell line, A375. Both instrumental techniques suggested the formation of inclusion complexes and the increase of thermal stability of artemisinin in complexes versus pure compound. Regarding the antioxidant activity evaluation of all samples, it was shown that this is significantly inferior in comparison to ascorbic acid, while the in vitro biological activity showed that inclusion complexes (CPX2 and CPX3) exerted an inhibitory effect on human melanoma cells growth, similar to the effect induced by artemisinin.