Interactions of Cyclodextrins with Dipalmitoyl, Distearoyl, and Dimyristoyl Phosphatidyl Choline Liposomes. A Study by Leakage of Carboxyfluorescein in Inner Aqueous Phase of Unilamellar Liposomes.

Abstract

The interaction of cyclodextrins (CDs) with L-alpha-dipalmitoyl phopsatidyl choline (DPPC), L-alpha-distearoyl phosphatidyl choline (DSPC), and L-alpha-dimyristoyl phosphatidyl choline (DMPC) unilamellar liposomes was investigated by the leakage of carboxylfluorescein (CF) entrapped in the inner aqueous phase of liposomes, at 25 degrees C (DPPC and DSPC liposomes) and at 5 degrees C (DMPC liposomes). The efficiency of CDs for CF leakage was remarkable in the order of heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD) > alpha-CD > heptakis (2,3,6-tri-O-methy)-beta-CD (TOM-beta-CD) from DPPC liposomes, in the order of DOM-beta-CD > TOM-beta-CD > alpha-CD from DSPC liposomes and in the order of alpha-CD > DOM-beta-CD > TOM-beta-CD from DMPC liposomes. The other CDs used in the present studies, beta-CD, 2-hydroxylpropyl beta-CD, and gamma-CD scarcely induced the CF leakage from above the three liposomes. From the profiles of % CF leakage, together with measurements of differential scanning calorimetry, it was found that hydrophobic DOM-beta-CD penetrates the matrix of the liposomes to interact with them as well as TOM-beta-CD, and that less hydrophobic alpha-CD exists at the surface of the membrane to interact with the liposomes. Further, it was found that the interaction of CDs with liposomes changes depending not only on the length of fatty acid chain of phospholipid (condensation force and hydrophobicity) but also the hydrophobicity and the cavity size of CD.

Interaction of Heptakis (2,3,6-Tri-<i>O</i>-methyl)-&beta;-cyclodextrin with Cholesterol in Aqueous Solution

“…12 The life time of the complexed species was approximately calculated using following Eqs. (8) and (9) 13) : (8) (9) where D e and D 0 represent the widths at half-height (Hz) of the signal in the presence of exchange and in the absence of exchange, respectively, and t and k represent mean life time and mean exchange rate constant, respectively. Also, t com.…”

“…For example, DOM-b-CyD penetrates the matrix of liposomes and extracts phospholipid from liposomes to form a soluble complex, whereas only a small amount of TOM-b-CyD penetrates the matrix of liposomes to remain there and therefore, TOM-b-CyD has very week ability to form a soluble complex with phospholipids. 7,8) For these reasons, TOM-b-CyD is used to alter membrane cholesterol content as mentioned above, although DOM-b-CyD is not used for this purpose. As another example, the formation constant of the complex between TOMb-CyD 9) and 8-anilino-1-naphthalenesulfonate (ANS) is smaller than that between DOM-b-CyD 10) and ANS.…”

β‐Cyclodextrin‐Mediated Removal of Soy Phospholipids from the Air–Water Interface

“…FA acyl chains are non-polar and have a cross-sectional diameter of *4.0 Å [17], which would likely facilitate their inclusion in the hydrophobic cavity (diameter = 6-6.5 Å ) of bCD. This assertion is supported by several experimental studies, which have shown that bCD can form complexes with lipids containing single or double alkyl chains of variable length [18][19][20][21][22][23][24][25].…”

Effect of Cyclodextrin Complexation on the Liposome Permeability of a Model Hydrophobic Weak Acid

“…This has prompted several investigators (16,(19)(20)(21)(22) to probe the effect of various cyclodextrins on membrane stability. Some cyclodextrins such as methyl-β-cyclodextrin can bind to lipids and alter their thermotropic properties, while other cyclodextrins such as HPβCD and SBEβCD do not appear to interact with the bilayer.…”

“…While interactions of some cyclodextrins with certain liposome components such as cholesterol have been reported (17,18), the reason for the observed biphasic release kinetics remains unclear. Certain cyclodextrins such as HPβCD have been found to have a negligible effect on the gel to liquid crystalline phase transition enthalpy or temperature (19,20) and to induce no significant leakage of entrapped markers (16,21,22). Therefore, such non-interacting cyclodextrins may be more useful as excipients for prolonged release liposomal suspensions.…”