Composition-tunable H-PC/LPC discoidal lipid assemblies: molecular packing, nanoscale organization, and permeation...

Discoidal membrane-like lipid assemblies provide a useful framework for linking lipid composition to nanoscale organization and interfacial transport, but practical solvent-avoiding routes from formulation-compatible phospholipids remain limited. Here, hydrogenated phosphatidylcholine (H-PC)/lysophosphatidylcholine (LPC) dispersions were prepared in the presence of 1,3-butylene glycol (BG) by a simple heating-stirring procedure that avoids organic solvents used in thin-film hydration. Varying the H-PC/LPC ratio revealed a composition window in which transparent nanoscale dispersions with apparent hydrodynamic diameters of 10-20 nm were obtained. TEM and ³¹P NMR analyses most clearly supported discoidal assemblies with bicelle-like features at intermediate LPC fractions, whereas lower LPC fractions yielded lamellar/vesicular aggregates and higher LPC fractions showed smaller, more isotropic aggregate states. DSC showed a decrease in the main endothermic transition temperature with increasing LPC fraction, consistent with composition-dependent thermotropic phase behavior and altered packing compatibility between H-PC-rich ordered domains and LPC-rich components. In Franz diffusion experiments using caffeine as a hydrophilic probe, H-PC/LPC dispersions showed higher permeation across Strat-M® membranes than a BG-matched lipid-free control. Compared with LPC-only formulations, the mixed H-PC/LPC series showed a clearer composition-dependent permeation profile, indicating that permeation behavior is associated with the nanoscale state of the mixed lipid dispersion rather than LPC content alone. A representative discoidal-assembly composition gave a numerically higher cumulative permeated amount across excised human skin. These results identify a practical route to composition-tunable H-PC/LPC lipid assemblies with discoidal, bicelle-like features and show that molecular packing and aggregate organization are linked to permeation behavior at biological interfaces.