Ethanol-enhanced permeation of phosphatidylcholine/phosphatidylethanolamine mixed liposomal membranes due to ethanol-induced lateral phase separation

Effects of ethanol on permeability of large unilamellar vesicles (ca. 160 nm in diameter), composed of dipalmitoyl phosphatidylcholine/dilauroyl phosphatidylethanolamine (DLPE) mixture, were studied by monitoring leakage of the fluorescent dye, calcein, entrapped in the inner aqueous phase of the vesicles. In the presence of 2.1 M ethanol, permeabilities of membranes in various phases were G (bilayer gel) phase > L (bilayer liquid-crystalline) phase with a high mole fraction of DLPE and (I (ethanol-induced interdigitated gel phase) + G) phase > (I + L) at 20 mol %DLPE. Arrhenius plots of the leakage rate constants demonstrated that the permeability was greater with 2.1 M ethanol than without ethanol, especially in the temperature above 33 degrees C, suggesting that the presence of ethanol can induce lateral phase separation of liposomal membranes and cause them to have a high permeability even if they are stable and have low permeability in its absence.