Roles of lipid polymorphism in intracellular delivery

Lipids, which adopt nonbilayer phases, have fascinated researchers as to th e functional roles of these components in biomembranes. In particular, lipi ds 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-destabi lizing properties. We will outline the molecular basis for the polymorphic phase behavior of lipids and highlight some of the uses of nonbilayer lipid s in the preparation of lipid-based delivery systems. In addition, a distin ction will be drawn between lipid-based systems which rely on the inclusion of nonbilayer lipids for activity, and systems which contain components wh ich actively promote formation of nonbilayer structure within biological me mbranes. (C) 2001 Elsevier Science B.V. All rights reserved.