Sodium hyaluronate-stabilized luteolin-loaded microemulsion gel: Interface-driven nanocarrier for enhanced skin...

Luteolin (LUT), a promising phytochemical for atopic dermatitis (AD) therapy, is limited by poor solubility and skin permeability in topical application. To address this, a novel LUT-loaded microemulsion-based (LUT-ME) gel was developed to facilitate drug delivery. The optimal LUT-ME formulation, obtained by a pseudo-ternary phase diagram and D-optimal mixture design, comprised 7.23 % glycerol triacetate, 34.56 % Smix, and 58.21 % water. DLS analysis showed a mean droplet size of 28.77 ± 0.31 nm and a PDI of 0.31 ± 0.04, while the zeta potential was -2.95 ± 0.68 mV and the drug loading reached 7.28 ± 0.05 mg/mL. Characterization by TEM, XRD, and FTIR demonstrated uniform droplet morphology, amorphous LUT dispersion, and good drug-excipient chemical compatibility. Notably, LUT-ME more significantly suppressed reactive oxygen species (ROS) and pro-inflammatory mediators in LPS-stimulated RAW264.7 cells compared to free LUT. Incorporation of sodium hyaluronate (SH) yielded a shear-thinning gel with favorable spreadability, good stability, and negligible skin irritation. Moreover, enhanced skin permeation of LUT-ME gel (2.09-fold vs LUT gel) in ex vivo studies contributed to its superior anti-inflammatory and histopathological effects in an AD mouse model. These results indicate that LUT-ME gel markedly improves the topical therapeutic efficacy of LUT against AD.