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

Abstract 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°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.