Interactions between cyclodextrins and cellular components: Towards greener medical applications?

Leclercq, Loïc

This different effect, observed for native CDs, has been explained by Ohtani et al. in 1989 [58] . As the membrane of erythrocytes is composed of proteins (43%) associated with lipids (49%) and carbohydrates (8%) and as the fraction of cholesterol is 25% of total membrane lipids [54], the proposed explanation is based on the specific interaction of natural CDs with the erythrocyte membrane components. Indeed, α-and β-CD are excellently suited to solubilize phospholipids and cholesterol, respectively, whereas γ-CD is generally less lipidselective. In more detail, the CD affinity for solubilizing various lipid components of the erythrocyte membranes are in the order γ-CD << β-CD < α-CD for phospholipids and α-CD < γ-CD << β-CD for cholesterol [58] . These findings are corroborated by the work of Leventis and Silvius which have reported that β-and γ-CD accelerate the rate of cholesterol transfer by a larger factor than they accelerate the transfer of phospholipid, whereas the opposite is true for α-CD [60] . The hemolytic properties of CDs are a general behavior not limited to human erythrocytes: All mammalian red blood cells are affected by the parent CDs. For instance, dog erythrocytes are also affected by native CDs in the order γ-CD < α-CD < β-CD [61] . Thus, the magnitude of the hemolytic activity observed for dog erythrocytes is consistent with the order of magnitude of human erythrocytes (see discussion above). However, the hemolytic activity is largely influenced by the substituents attached to the CDs. The presence of hydrophilic substituents (e.g., glucosyl, 2-hydroxypropyl, 3-hydroxypropyl, maltosyl, sulfate, sulfobutyl ether, etc.) reduces the hemolytic activity in comparison with the parent CDs while the lipophilic ones (e.g., methylated CDs) demonstrate the strongest hemolytic activities [62] . As for parent CDs, these differences are ascribed to the different solubilization effects of lipid components and their sequestration in the external aqueous phase.