Abstract
The protective mechanism of cyclodextrins (α-, β-, and γ-CyDs) on the imipramine (IMP) -induced hemolysis was discussed on the basis of inclusion complexation. Inclusion complexation of IMP with CyDs in isotonic solution was assessed by ultraviolet and circular dichroism spectroscopies. CyDs were found to protect the human erythrocytes from the hemolysis and shape changes induced with IMP, depending upon the magnitude of stability constant of IMP-CyD complexes (β->γ->α-CyD). The uptake of IMP into erythrocytes was also reduced by the addition of CyDs in the order of, β->γ->α-CyD. The affinity of the complexed form of IMP to erythrocytes was proven to be negligibly small compared with that of the free IMP. The poor affinity of the complex can be explained by the decrease in surface activity and/or membrane permeability of IMP by encapsulation in hydrophilic and bulky CyD molecule. These results suggest that the protective effect of CyDs on the IMP-induced hemolysis is mainly caused by the reduction in the effective hemolytic concentration of IMP through inclusion complexation rather than the stabilizing action of CyDs on the erythrocyte membrane.
