Roles of lipid polymorphism in intracellular delivery

Lipids, which adopt nonbilayer phases, have fascinated researchers as to the functional roles of these components in biomembranes. In particular, lipids capable of adopting the hexagonal H(II) phase have received considerable attention because of the observation that such lipids can promote membrane fusion. In the rational design of lipid-based delivery systems, H(II) phase lipids have been employed to endow systems with fusogenic, membrane-destabilizing properties. We will outline the molecular basis for the polymorphic phase behavior of lipids and highlight some of the uses of nonbilayer lipids in the preparation of lipid-based delivery systems. In addition, a distinction will be drawn between lipid-based systems which rely on the inclusion of nonbilayer lipids for activity, and systems which contain components which actively promote formation of nonbilayer structure within biological membranes.