Drug delivery applications of non-lamellar liquid crystalline phases and nanoparticles

Lipid liquid crystal (LC) phases are fascinating structures formed spontaneously in aqueous media through molecular self-assembly. The resulting three-dimensional architectures with supra-molecular order are governed by the effective molecular geometries of the participating lipid building blocks. LC structures vary from normal “oil-in-water” phases to reversed “water-in-oil” phases, where the lipid and aqueous domains can be isolated, continuous or biocontinuous depending on the phase morphology. As is intuitively understood, this imposes different degrees of restriction to diffusive transport within LC phases; a property that can be effectively utilized for controlling the release of active pharmaceutical ingredients (API) in drug products. Aside from controlling release, LC phases can also be used for protecting sensitive substances such as peptides and proteins from enzymatic degradation, and for solubilization of sparingly soluble compounds into the lipid and/or aqueous nano-domains. LC phases can furthermore, with the aid of swelling and stabilization aids such as amphiphilic surfactants and copolymers, be fragmented into well-defined and kinetically stable nanoparticles (LCNP) with more or less retained inner phase structure. Due to their often very high solubilizing and encapsulating abilities, LCNPs are interesting carrier systems for a broad range of API, from small sparingly soluble substances to larger peptides or proteins. Here we discuss the interplay between structure and function of LC systems and also their different uses in commercial and pipeline products.