EVALUATION OF THE CYTOTOXICITY OF CYCLODEXTRINS AND HYDROXYPROPYLATEDDERIVATIVES

The haemolytic effect toward human erythrocytes and the cytotoxicity t oward P388 cells of the three natural cyclodextrins and their hydroxyp ropylated derivatives have been compared. The cytotoxicity of the six cyclodextrins toward these two cell types follows a similar pattern, a nd the curve parameters are generally of the same order of magnitude f or both cell types in spite of the biological differences. The in vitr o cytotoxic effect decreases in the order beta CD > alpha CD > gamma C D and HP beta CD > HP gamma CD greater than or equal to HP alpha CD. T hese results showed that phenomena involved in cyclodextrin cytotoxici ty are not specific to the cell type, and bare out the hypothesis of d estruction of membranes by the removal of basic membrane components. M oreover, they demonstrated the influence of parameters other than CD c oncentration, i.e., the presence of serum components, or the density o f the cells, which can dramatically influence the cytotoxic effect of CDs. In fact, the cytotoxicity of a cyclodextrin is determined by the relative proportion of cellular and extracellular molecules likely to be included and cyclodextrins.