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

Leclercq, Loïc

As the hemolysis is attributed to the removal of erythrocyte membrane components, particularly phospholipids and cholesterol, the value of the binding constants between CDs and lipids can be very relevant. To the author's knowledge there is only one paper in the literature that describes the binding constants between CDs (α-or γ-CD) and short phospholipids (i.e., diheptanoylphosphatidylcholine, DHPC) [63] . In this study, the association constants were estimated from 1 H NMR measurements. The results proved that the K 1 values are in the order α-CD < γ-CD while the K 2 values are in the order γ-CD < α-CD. This behavior was attributed to the large cavity of γ-CD which is able to incorporate both alkyl chains of DHPC simultaneously. In contrast, the formation of a 1:2 inclusion complex with α-CD is easier than with γ-CD. These findings are corroborated by Fauvelle and co-workers who reported that α-CD has the strongest affinity to phospholipids (e.g., phosphatidylinositol) [64, 65] . In 2000, Nishijo et al. studied the interactions of various CDs with dipalmitoyl, distearoyl, and dimyristoylphosphatidylcholine liposomes. This study highlights that the liposome-CD interaction depends on the length of the fatty acid chain of the phospholipid, the cavity size, and the nature of the substituents at the CD [66] . In the literature, the binding constant between cholesterol and β-CD was estimated around 1.7 × 10 4 M −1 from a solubility method [67, 68] . This value proves the good stability of the inclusion complex because of the driving force of complexation: hydrophobic interaction. Despite there is no information on the binding constant observed for the inclusion of cholesterol in γ-CD, the cavity internal diameter of the β-CD and its derivatives perfectly matches the size of the sterol molecules contrary to γ-CD (too large) [69, 70] . Moreover, the positive correlation observed between the hemolytic activities of various modified CDs and their ability to solubilize cholesterol reveal that HP-β-CD was shown to be a more efficient cholesterol-acceptor molecule than HP-γ-CD. This is apparently due to the diameter of its internal cavity that matches the size of this molecule. Finally, it is noteworthy that all CDs lose their abilities to induce hemolysis, when their cavities are occupied with guest molecules due to a reduced interaction with the erythrocyte membranes [71] . All these observations support the aforementioned affinities of α-CD for phospholipids and of β-CD for cholesterol.