Omega-3 polyunsaturated fatty acids
(ω-3 PUFAs) are bioactive
lipids with considerable impact in medicine and nutrition. These compounds
exert structuring effects on the cellular membrane organization, regulate
the gene expression, and modulate various signaling cascades and metabolic
processes. The purpose of the present work is to demonstrate the structural
features of ω-3 PUFA-containing three-dimensional supramolecular
lipid assemblies suitable for pharmaceutical applications that require
soft porous carriers. We investigate the liquid crystalline structures
formed upon mixing of eicosapentaenoic acid (EPA, 20:5) with the lyotropic
nonlamellar lipid monoolein and the formation of multicompartment
assemblies. Starting with the monoolein-based lipid cubic phase, double
membrane vesicles, cubosome precursors, sponge-type particles (spongosomes),
mixed intermediate nonlamellar structures, and multicompartment assemblies
are obtained through self-assembly at different amphiphilic compositions.
The dispersions containing spongosomes as well as nanocarriers with
oil and vesicular compartments are stabilized by PEGylation of the
lipid/water interfaces using a phospholipid with a poly(ethylene glycol)
chain. The microstructures of the bulk mixtures were examined by cross-polarized
light optical microscopy. The dispersed liquid crystalline structures
and intermediate states were studied by small-angle X-ray scattering,
cryogenic transmission electron microscopy, and quasielastic light
scattering techniques. They established that PUFA influences the phase
type and the sizes of the aqueous compartments of the liquid crystalline
carriers. The resulting multicompartment systems and stealth nanosponges
may serve as mesoporous reservoirs for coencapsulation of ω-3
PUFA (e.g., EPA) with water-insoluble drugs and hydrophilic macromolecules
toward development of combination treatment strategies of neurodegenerative
and other diseases.