Research on Preparation of Tranexamic Acid Nanoemulsion Gel and Its Transdermal Performance in Vitro

OBJECTIVE  To construct tranexamic acid(TXA) nanoemulsion gel and preliminarily elucidate its transdermal mechanism using TXA as a model drug.

METHODS  The TXA nanoemulsion was prepared by shear-stirring emulsification method, and TXA nanoemulsion gel was prepared by physical cross-linking method. The preparation process was evaluated based on particle size, Zeta potential, encapsulation efficiency, the polydispersity index(PDI) and appearance. Process optimization was conducted through equilibrium solubility, pseudo-ternary phase diagram and Box-Behnken response surface design. The formulation was characterized by transmission electron microscopy and nanoemulsion staining. In vitro transdermal permeation and its effects on skin structure were investigated using Franz diffusion cell method, attenuated total reflectance Fourier-transform infrared spectroscopy(ATR-FTIR), and HE staining.

RESULTS  The prepared oil in water(O/W)-type TXA nanoemulsion appeared as a light blue liquid with a particle size of (68.29±0.11)nm, PDI of 0.148±0.07, encapsulation efficiency of (98.74±0.03)%, pH of 6.95, and exhibited good stability. The nanoemulsion gel appeared as a colorless, transparent semi-solid with a uniform and fine texture. In vitro transdermal results showed that the cumulative permeation of the TXA nanoemulsion gel was 199.74 μg·cm⁻² with sustained-release properties, and the intradermal retention was 97.6821 µg·cm⁻². ATR-FTIR analysis indicated that the TXA nanoemulsion gel enhanced the fluidity of the lipid bilayers in the stratum corneum, thereby reducing the skin barrier function. HE staining revealed intact skin structure in the control group, while both the TXA nanoemulsion and TXA nanoemulsion gel groups exhibited structural changes with increased intercellular gaps. ATR-FTIR and HE staining results demonstrated that the TXA nanoemulsion and TXA nanoemulsion gel facilitated transdermal delivery by altering the conformation of the stratum corneum.

CONCLUSION  The prepared TXA nanoemulsion gel exhibits stable physical properties, excellent drug release and transdermal performance, providing reference for the application of TXA.