INTERACTION OF NATURAL AND MODIFIED BETA-CYCLODEXTRINS WITH A BIOLOGICAL MEMBRANE MODEL OF DIPALMITOYLPHOSPHATIDYLCHOLINE

Lipid vesicles made up of dipalmitoyl-sn-glycero-3-phosphocholine (DPP C) were used as a biological membrane model to investigate the interac tion between natural and modified beta-cyclodextrins and these membran e bilayers. Differential scanning calorimetry was used to study the th ermotropic behavior of the DPPC vesicles and any change caused by the presence of cyclodextrins. The presence of dimethyl-beta-cyclodextrin (DM-beta-CyD) triggered a reduction in the enthalpy values related to the main transition peak from gel state to liquid crystal phase of DPP C aqueous dispersions, as a function of the DM-beta-CyD molar fraction : the larger the amount of DM-beta-CyD, the greater the reduction in D elta H values. This effect was probably due to the ability of DM-beta- CyD to extract and to complex the DPPC molecules forming the phospholi pid vesicles. The presence of beta-cyclodextrin (beta-CyD) or hydroxyp ropyl-beta-cyclodextrin (HP-beta-CyD) caused no particular alteration in the thermotropic parameters of DPPC vesicles, whereas trimethyl-bet a-cyclodextrin (TM-beta-CyD) at molar fractions higher than 0.12 cause d broadening of the transition peak due to a possible interaction with the hydrophobic part of the bilayers. Experiments on DPPC-cholesterol (10 mol%) vesicles showed the capability of beta-CyD and TM-beta-CyD to extract cholesterol from the ordered bilayer structures, triggering an alteration in the lipid constituents of the membranes. HP-beta-CyD caused no variation in the thermotropic parameters of the DPPC-choles terol (10 mol%) vesicles. The findings show that HP-beta-CyD seems the most suitable molecular drug carrier for in vivo administration. (C) 1996 Academic Press, Inc.