Does a cluster phase in polyion-liposome colloidal suspensions exist? An integrated experimental overview

Although the properties of mesoscopic charged complexes, originating by the self-assembling of polyions onto oppositely charged particles, are been extensively investigated, both experimentally and theoretically, less attention has been addressed towards the existence of an equilibrium cluster phase in low-density colloidal suspensions, where particles maintain their integrity and polyions act as an electrostatic glue. The self-assembling of lipidic vesicles into mesoscopic aggregates induced by polyions is a hierarchical process where, at different basic levels, aggregates arrange themselves to form superstructures, giving rise to multi-lamellar complexes or honeycomb structures in which polyions are more or less intercalated between the lipid bilayers. This reorganization becomes relevant in many biological important processes such as drug delivery. However, besides these rather complex structural rearrangements, at a lower hierarchy level, clusters formed by intact vesicles, stuck together by oppositely charged polyions, may exist. These equilibrium clusters, which we call "intermediate" aggregates, can be considered as a new class of colloids with a rich and not yet completely understood phenomenology. In this review, we will refer to a specific example and will present a well-documented experimental evidence of the formation of equilibrium clusters composed by positively charged liposomes built up by DOTAP, stuck together by a simple highly charged linear polyion (polyacrylate sodium salt). These structures, governed by a balance between long-range electrostatic repulsion and short-range attraction, give rise to the formation of relatively large, equilibrium clusters whose size and overall charge can be continuously tunable by simple environmental parameters. Under appropriate experimental conditions, in a long time limit, these liposome clusters may further evolve towards a different structural arrangement, giving account for the supramolecular structures of polyion-liposome complexes, such as those observed in DNA-lipid complexes. (C) 2006 Elsevier B.V. All rights reserved.