''Sponge" nanoparticle dispersions in aqueous mixtures of diglycerol monooleate, glycerol dioleate, and polysorbate 80

Lipid nanoparticles of nonlamellar lyotropic phases have a wide solubilizing and encapsulating spectrum for a range of substances thanks to their nanostructured interior featuring both lipophilic and hydrophilic domains. As a consequence, these systems have emerged as promising drug delivery systems in various pharmaceutical and diagnostic applications. Here we present the phase behavior and dispersion properties of a novel three-component lipid system composed of diglycerol monooleate (DGMO), glycerol dioleate (GDO), and polysorbate 80 (P80) which shows several advantageous features relating to drug delivery applications including: spontaneous dispersion formation with a narrow size distribution and tunable particle phase-structure. The obtained phase diagram shows the presence of lamellar (L-alpha), hexagonal (H-2), and reverse bicontinuous cubic (V-2) liquid crystalline phases and an inverse micellar (L-2) solution. A particularly interesting observation is the presence of a phase region where two liquid phases coexist, most likely the L-2 and L-3 ("sponge phase"). These two phase structures appear also to coexist in the submicron particles formed in the dilute water region, where the L-3 element appears to stabilize nanoparticles with inner L-2 structure. Increasing the fraction of the dispersing P80 component results in the growth of the more water rich L-3 "surface phase" at the expense of the size of the inner L-2 core.