Nanostructuring and Antioxidant Activity of Nanotherapeutics Designed by Self-Assembly of Natural Lipids and Phytochemicals

Lyotropic liquid crystalline nanostructures formed by self-assembly in an aqueous medium are of fundamental interest and crucial for therapeutic applications, encapsulation of nutraceuticals, tissue engineering, and diagnostics. The biomimetic lipid bilayer building blocks impart biodegradable properties and low toxicity of the created nanoassemblies. The question of synergistic or quenching effects on the resulting bioactivity arises from the coencapsulation of multiple antioxidants (<i>e.g.,</i> vitamin E (VitE), curcumin (CU), or coenzyme Q₁₀) in nanocarriers of mixed nonlamellar-phase lipids (e.g., amphiphilic monoglycerides or plasmalogens with long polyunsaturated fatty acid (PUFA) chains). The response to this question should favor phytochemical-based therapies against oxidative stress and inflammatory disorders using sustainable nanomedicines. Herein, we investigate the nanodispersion of multicomponent antioxidant/lipid mixtures using the copolymer Pluronic F127 and three PEGylated amphiphiles (TPGS-PEG₁₀₀₀, MO-PEG_2000, and DSPE-PEG₂₀₀₀). The purpose is to establish possible relationships between the amphiphilic pharmaceutical compositions, structural stability, degradability in the biological cell culture medium, and the effects on antioxidant activity. The structures and the topologies of the phytochemical-loaded mesophases were revealed by synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy imaging. We found that encapsulated antioxidants (CU, Q_10, or VitE) fine-tune the lipid bilayer properties and the nanostructure of the self-assembled systems to form lamellar (L), inverted hexagonal (H_II), or cubic (<i>Im3m</i>) liquid crystalline phases. The results demonstrated that the composition of the nanoassemblies (lipids, dispersing agents, and antioxidants) governs the structural organization through changes in the interfacial curvature and miscibility effects. A minimal toxicity of the nanoassemblies was observed <i>in vitro</i> using the human neuroblastoma cell line (SH-SY5Y). The biodegradability/stability of the nanodispersions was linked with gradual dynamic changes in nanoparticle size distribution in the biological cell culture medium (DMEM). The established enhanced reactive oxygen species (ROS)-scavenging activity of the liquid crystalline nanoformulations is of interest for developing safe pharmaceutical nanosystems for multitargeted delivery of poorly soluble phytochemicals.