Bicontinuous cubic phase: a model for investigating the effects on a lipid bilayer due to a foreign substance

Biological effects of foreign substances are usually caused by their interaction within lipid bilayers with the membrane lipids. It is therefore desirable in many situations to determine the effects and the partition of xenobiotic substances, as well as drugs, added to amphiphile-water systems. Bicontinuous cubic liquid crystals provide three-dimensional isotropic matrices with symmetries easily obtained by X-ray diffraction, and were shown to be a useful tool for an initial investigation of the molecular properties possessed by a foreign substance. The concept is illustrated by adding the transdermal penetration enhancer Azone (n-dodecyl-caprolactam) to V2-phases in the glycerol monooleate (GMO)-water system. The weakly polar, water immiscible, Azone is known to favour reversed types of phases in liquid crystals. In the present investigation, Azone was shown to prefer the lipid bilayer interior, with about 19% anchored in the lipid-water interfacial region. Some dependence of its location on water concentration was indicated. The unexpected swelling behaviour of monoacylglycerols in water (L2-->L alpha-->V2) were postulated to result from the lipids changing their polar headgroup conformation, thus allowing for an increase in packing parameter upon increasing the water content.