Composition-Switchable Liquid Crystalline Nanostructures as Green Formulations of Curcumin and Fish Oil

Abstract

Green compositions and processes for fabrication of dual- and multiloaded nanocarriers with an antioxidant functionality and neuroprotective, cardioprotective, antiviral, and antiproliferative activities are of broad interest for innovations in pharmaceutics and nutraceutics. Coencapsulation of curcumin (studied as a key multipurpose phytochemical antioxidant) with ω-3 polyunsaturated fatty acids (PUFAs) (studied as active ingredients of natural fish oil) may increase the oxidative stability of self-assembled formulations aiming at the development of “food drugs” and prevention of disease progression in various pathological states. The objective of this work is to prepare self-assembled lyotropic liquid crystalline nanostructures as dual-loaded biodegradable carriers of ω-3 PUFA-fish oil and curcumin. A detailed structural phase diagram of a ternary [monoolein-PEGylated lipid mixture]/[fish oil-curcumin]/water system is created. A composition-mediated switch between nanostructures of different topologies and polymorphic states is achieved through varying the ratios between the amphiphilic monoglyceride ingredient, fish oil, and water, which yielded cubic, sponge, and lamellar mesophases of tunable nanoscale repeat spacings. Synchrotron small-angle X-ray scattering (SAXS) studies are performed with the lyotropic liquid crystalline nanostructures along compositional dilution lines. The temperature effect is examined at 22 and 5 °C with regard to preparation conditions and mesophase stability on storage. Bulk mesophases are dispersed into lipid nanoparticles at 22 °C, the structures and topologies of which are revealed by SAXS and cryo-transmission electron microscopy imaging. New knowledge about the controlled multicomponent supramolecular assembly and the achieved stabilization of low-temperature cubic phases (hydrated in 5 wt % d-(+)-glucose) should facilitate the development of cost-effective, stable, and safe delivery systems of weakly soluble natural antioxidant compounds coencapsulated with ω-3 PUFA oils.