Cyclodextrins are widely used excipients, composed of glucopyranose units with a cyclic structure. One of their most important properties, is that their inner cavity is hydrophobic, while their surface is hydrophilic. This enables them for the complex formation with lipophilic molecules. They have several applications in the pharmaceutical field like solubility enhancers or the building blocks of larger drug delivery systems. On the other hand, they have numerous effects on cells or biological barriers. In this review the most important properties of cyclodextrins and cyclodextrin-based drug delivery systems are summarized with special focus on their biological activity.

Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, the concentration of α-cyclodextrin used may be very high in these cases, and its toxic attributes have to be seriously considered. The objective of this study was to investigate the cytotoxicity of various, differently substituted α-cyclodextrin derivatives and determine relationship between the structures and cytotoxicity. Three different methods were used, viability tests (MTT assay and Real Time Cell Electronic Sensing on Caco-2 cells) as well as hemolysis test on human red blood cells. The effect of α-cyclodextrin derivatives resulted in concentration-dependent cytotoxicity, so the IC50 values have been determined. Based on our evaluation, the Real Time Cell Electronic Sensing method is the most accurate for describing the time and concentration dependency of the observed toxic effects. Regarding the cytotoxicity on Caco-2 cells, phosphatidylcholine extraction may play a main role in the mechanism. Our results should provide help in selecting those α-cyclodextrin derivatives which have the potential of being used safely in medical formulations.