Differential Effects of Sulfate and Sulfobutyl Ether of β-Cyclodextrin on Erythrocyte Membranes in Vitro

Abstract

The hemolytic activity of β-cyclodextrin (β-CyD) on rabbit erythrocytes was reduced by the introduction of negatively-charged groups onto the hydroxyls of β-CyD; the membrane disrupting abilities decreased in the order of β-CyD > 2-hydroxypropyl-β-CyD (HP-β-CyD) > sulfobutyl-β-CyD (SB-β-CyD) >> β-CyD sulfate (S-β-CyD). Under pre-hemolytic concentrations, both β-CyD and SB-β-CyD induced shape changes of membrane invagination on the erythrocytes. In sharp contrast, S-β-CyD showed biphasic effect on the shape of the erythrocytes; i.e. the crenation at relatively low concentrations and the invagination at higher concentrations. The S-β-CyD-induced membrane crenation arose from a direct action on the membranes rather than cell metabolism-mediated effects. Unlike β-CyD, S-β-CyD was found to bind to the erythrocytes and may be confined to the outer surface of the membrane bilayer, which may expand the exterior layer relative to the cytoplasmic half, thereby inducing the cells to crenate. On the other hand, the membrane invagination mediated by the three β- CyDs was initiated by extracting specific membrane lipids from the cells, depending upon their inclusion abilities, subsequently leading to the lysis of the cells. These results indicate that SB-β-CyD and S-β-CyD interact with the erythrocyte membranes in a differential manner and possess lower membrane disrupting abilities than the parent β-CyD and HP-β-CyD.