Unsaturation-driven nanoscale structural remodeling of thermoresponsive Triton X-114 mixed micelles for enhanced curcumin delivery.

Abstract

Thermoresponsive mixed surfactant systems offer versatile platforms for designing adaptive nanostructures with tunable interfacial and enhanced drug-delivery performance. The present sets of studies systematically elucidated the unsaturation-directed nanoscale structural evolution of Triton X-114 (TX-114) mixed assemblies induced by the monounsaturated surfactant sodium oleate (NaOl) and the diunsaturated surfactant sodium linoleate (NaLOl). A comprehensive multitechnique investigation combining the classical physicochemical methods, scattering techniques, spectroscopic analyses and density functional theory (DFT) calculations unveiled the pivotal role of molecular unsaturation in governing interfacial packing, hydration, non-covalent interactions, and aggregate curvature in thermoresponsive nanoassemblies. Incorporation of NaOl and NaLOl into TX-114 induced an unusual 'double cloud point' phenomenon, depicting the co-occurrence of compositionally distinct nanoaggregates. Small-angle neutron scattering (SANS) and transmission electron microscopy (TEM) measurements divulged concentration-dependent micellar transitions arising from the delicate balance between hydrophobic interactions and electrostatic repulsion. Nuclear Overhauser effect spectroscopy (NOESY) and Fourier transform infrared (FTIR) spectroscopy further uncover distinct spatial molecular organization and modulation of the hydrogen-bonding network within the hydration shell of the mixed nanoaggregates. DFT calculations together with non-covalent interaction-reduced density gradient (NCI-RDG) analysis demonstrated comparatively stronger intermolecular stabilization and greater electronic softness for TX-114 + NaLOl assemblies. Notably, the structurally remodeled nanoaggregates exhibited significantly enhanced curcumin solubilization, sustained in vitro drug release, improved antioxidant efficiency, and anti-inflammatory activity, underscoring their potential as efficient nanocarriers for hydrophobic therapeutics. These outcomes unveil molecular unsaturation as a powerful regulator of thermoresponsive nanoscale self-assembly and provide fundamental design principles for developing responsive surfactant-based nanocarriers for advanced drug-delivery applications.

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