Development of skin-permeable flexible liposome using ergosterol esters containing unsaturated fatty acids

Ergosterol (Ergo) and cholesterol contribute to performances of liposomes by increasing membrane packing density and physical stability. However, as these sterols can reduce membrane flexibility, they can lower skin permeability of liposomes. We synthesized ergosterol ester (Ergo-Est) containing unsaturated fatty acid different from Ergo in size and physical properties. In this work, we investigated effects of Ergo-Est and Ergo on physical properties of liposomes. We incorporated Ergo, Ergo-oleate (EO^18:1), Ergo-linoleate (EL^18:2), and Ergo-linolenate (ELn^18:3) into the liposomal membrane of egg phosphatidylcholine and soybean lecithin. Ergo-Est did not reduce membrane fluidity as much as Ergo. Nevertheless, Ergo-Est increased membrane packing density and physical stability of liposomes. EL^18:2 and ELn^18:3 almost maintained membrane flexibility and skin permeability of liposomes, while Ergo significantly reduced them. Skin permeation test demonstrated that EL^18:2 and ELn^18:3 liposomes permeated to the dermis, whereas Ergo liposome mostly remained in the stratum corneum. This is the first report to show that EL^18:2 and ELn^18:3 can be efficient sterol compounds for flexible liposome formulation.