Structural analysis of “flexible” liposome formulations: new insights into the skin-penetrating ability of soft nanostructures

Abstract

Self-assembled nanocontainers that can penetrate the protective barrier of skin could prove useful for the needle-free delivery of chemicals, drugs or vaccines into the skin. The main examples of these are the so-called “flexible liposomes”, which are mixtures of lipids and detergents. In vitro experiments by numerous researchers have confirmed the skin-penetrating ability of these structures, which is believed to involve the squeezing of flexible bilayers through the pores in the stratum corneum. Here, we reexamine the structure of “flexible” liposome formulations and show that these are actually mixtures of liposomes and micelles. These findings are reinforced through a combination of small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). We believe that our new findings necessitate a new mechanism for the penetration of soft assemblies into the skin. Several possibilities in this regard are considered, including one in which micelles facilitate the dynamic exchange of amphiphiles between liposomes and/or lipid bilayers.