Formation of Liquid Ordered Lamellar Phases in the Palmitic Acid/Cholesterol System

The phase behavior of the palmitic acid (PA)−cholesterol system in aqueous buffer at pH 5.5 has been investigated using infrared spectroscopy and 2H NMR spectroscopy of both chain deuterated PA and partially deuterated cholesterol. The results indicate that at temperatures below 50 °C, both lipids exist in a crystalline phase and are not miscible. However, we report the formation of a lamellar liquid ordered (lo) phase upon heating. In this phase, the acid and cholesterol molecules experience an axial symmetric motion while the acid acyl chains are conformationally ordered. Despite this unusual composition, the lo phase formed by PA−cholesterol exhibits similar properties to the phospholipid−cholesterol lo phases. The acyl chain order, the thermal expansivity of the bilayer, and the orientation and the dynamics of cholesterol are similar to those previously measured on phospholipidic lo phases. A temperature−composition diagram is proposed for the PA−cholesterol system. This diagram includes the presence of a eutectic with a PA/cholesterol molar composition of 30:70. It is proposed that melted palmitic acid provides a nonpolar environment for the solubilization of cholesterol and the latter induces a straightening of the fatty acid chains, promoting a molecular order compatible with bilayer formation. The implications of these findings in the understanding of the structure of the stratum corneum and in the development of non-phospholipidic liposomes are discussed.