Interactions of Cyclodextrins with DPPC Liposomes. Differential Scanning Calorimetry Studies.

Abstract

The interaction of cyclodextrins (CDs) with dipalmitoylphosphatidylcholine (DPPC) liposomes has been studied using differential scanning calorimetry (DSC). The phase transition temperature and the enthalpy change due to the gel-to-liquid crystalline phase transition of the liposomes were measured in the presence of alpha-CD, beta-CD, gamma-CD, heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD), heptakis (2,3,6-tri-O-methyl)-beta-CD (TOM-beta-CD) and 2-hydroxylpropyl beta-CD, respectively. The effects on the change of enthalpy of the transition temperature were remarkable in the order of DOM-beta-CD > alpha-CD > TOM-beta-CD. The residual CDs caused scarcely detectable changes in the enthalpy changes and the transition temperatures. In order to clarify the DSC curves in the presence of the CDs mentioned above, the type of interactions which occurred between CDs and DPPC liposomes were studied. Consequently, it was found that DOM-beta-CD forms a soluble complex and alpha-CD forms an insoluble complex with DPPC liposomes, whereas only a slight amount of TOM-beta-CD was suggested to penetrate the matrix of the liposomes.

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

“…These results suggest that HPβCD is entrapped only in the intravesicular aqueous compartment and does not bind significantly to the liposome membrane. This is consistent with previous observations (16,19,20,22) that reported a lack of interaction between HPβCD and gel phase lipid bilayers.…”

“…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.…”

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

“…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.…”

A Moderate Interaction of Maltosyl-&alpha;-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin

“…In addition, a-CyD is reported to interact with phosphatidylinositol strongly, but not phosphatidylcholine. 26,27) Furthermore, Miyajima et al 28) and Nishijo et al 29) reported that a-CyD sequesters DPPC molecules from the liposomes and forms an inclusion complex with DPPC out of a membrane matrix. Thus, the mode of the interactions between a-CyD and G 2 -a-CyD and lipids in the biological membranes seems to be complicated.…”

“…The cells (passages [28][29][30][31][32][33][34][35][36][37][38] were grown in DMEM supplemented with 10% heat-inactivated FCS, 1% non-essential amino acids, 2 mM L-glutamine, 0.45% D-glucose, 100 units/ ml penicillin G, 100 mg/ml streptomycin in a humidified atmosphere containing 5% CO 2 and 95% air at 37°C. Subconfluent monolayers were cultured every 5 d by treatment with 0.05% trypsin and 0.2% EDTA in phosphate-buffered saline (PBS).…”