Solute effects on the colloidal and phase behavior of lipid bilayer membranes: ethanol-dipalmitoylphosphatidylcholine mixtures

Abstract

By means of the scanning differential calorimetry, x-ray diffractometry, and the dynamic light scattering, we have systematically studied the phase and packing properties of dipalmitoylphosphatidylcholine vesicles or multibilayers in the presence of ethanol. We have also determined the partial ternary phase diagram of such dipalmitoylphosphatidylcholine/water/ethanol mixtures. The directly measured variability of the structural bilayer parameters implies that ethanol binding to the phospholipid bilayers increases the lateral as well as the transverse repulsion between the lipid molecules. This enlarges the hydrocarbon tilt (by up to 23 degrees) and molecular area (by < or = 40%). Ethanol-phospholid association also broadens the interface and, thus, promotes lipid headgroup solvation. This results in excessive swelling (by 130%) of the phosphatidylcholine bilayers in aqueous ethanol solutions. Lateral bilayer expansion, moreover, provokes a successive interdigitation of the hydrocarbon chains in the systems with bulk ethanol concentrations of 0.4-1.2 M. The hydrocarbon packing density as well as the propensity for the formation of lamellar gel phases simultaneously increase. The pretransition temperature of phosphatidylcholine bilayers is more sensitive to the addition of alcohol (initial shift: delta Tp = 22 degrees C/mol) than the subtransition temperature (delta Ts reversible 5 degrees C/mol), whereas the chain-melting phase transition temperature is even less affected (delta Tm = 1.8 degrees C/mol). After an initial decrease of 3 degrees for the bulk ethanol concentrations below 1.2 M, the Tm value increases by 2.5 degrees above this limiting concentration. The gel-phase phosphatidylcholine membranes below Tm are fully interdigitated above this limiting concentration. The chain tilt on the fringe of full chain interdigitation is zero and increases with higher ethanol concentrations. Above Tm, some of the lipid molecules are solubilized by the bound ethanol molecules. More highly concentrated ethanol solutions (> 7 M) solubilize the phosphatidylcholine bilayers with fluid chains fully and result in the formation of mixed lipid-alcohol micelles.

Phase behavior of selected artificial lipids

“…GIXD experiments have shown that the effective area per head group decreases with an increase in ethanol concentration leading to a reduction of the chain tilt angle. The influence of ethanol on self-assembled aggregates of phospholipid molecules has been reported in [33][34][35][36][37][38][39]. In these investigations, lipid bilayers dispersed as unilamellar or multilamellar vesicles in an aqueous solution have been used.…”

Ethosomes: versatile vesicular carriers for efficient transdermal delivery of therapeutic agents

“…The effect of ethanol on lipid systems came into existence during early 1990s. Vierl et al (1994) reported the investigative account of phase and packing properties of dipalmitoylphosphotidyl choline vesicles or multi-bilayers in the presence of ethanol, and then employment of high alcohol content was commenced by Touitou (Touitou, 1996;Touitou et al, 1997). The petite summary of numerous investigative literatures indicates that ethanol basically fluidizes and engorges the rigidly fixed lipid multilayer system of the stratum corneum lipids by reducing its T m , incorporation of high concentration of ethanol in ethosomes makes lipid vesicular membrane less densely crammed which provides warmness and malleability to them resulting in the formation of deformable and flexible vesicular system which could easily pierce through tiny openings formed in the disturbed SC lipids more deeply in contrast to other vesicular systems (Martin & Lloyd, 1992;Touitou, 1998).…”

“…The earlier pressure results in augmentation of an ethanol dependent change of the area per molecule whereas latter leads to excessive swelling of phosphatidylcholine bilayers in the aqueous ethanol solutions. As a result of which ethanol can induce hydrocarbon inter-digitation and increases inter-membrane separation in the gel phase plus ethanol also widens the interface and by doing so increases the scope and series of the lipid head group solvation (Vierl et al, 1994). This feature of ethanol got a breakthrough in 1996 where it gets a platform of formulation consisting phospholipid, double distilled water (DDW) and propylene glycols (PG) etc, and the visage of ethosomes emerged (Touitou, 1996).…”

Mesoscopic Simulations of Biological Membranes

“…To study the effect of these molecules on the properties studies on various model membranes have been carried out by various groups [66,[71][72][73][74][75][76]. These studies show that at low temperatures adding alcohol leads the formation of an interdigitated or L βI phase in stead of the commonly formed L c or L β (gel phases).…”