2025, Vol. 29 ›› Issue (28): 6061-6069

Functionalized self-assembled micelles enhance effect of tranexamic acid in treatment of cutaneous hyperpigmentation

Qi Junlong, Liu Junyi, He Yuzhou, Qiang Wei, Zhang Shiying, Liu Qiao, Zhu Hongda   

Abstract: BACKGROUND: Topical administration of tranexamic acid can be used for anti-skin pigmentation, but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically, and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.
OBJECTIVE: To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.
METHODS: The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials. The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction. The nanoscale properties and stability of self-assembled drug-loaded micelles were tested, and their transdermal permeability was evaluated, and their biocompatibility and cellular effects were investigated.
RESULTS AND CONCLUSION: (1) Functional self-assembled drug-carrying micelles with average particle size of (176.27±5.23) nm, polydispersity coefficient of 0.23±0.02, and the Zeta potential of (-25.67±0.98) mV had good stability. The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were (20.03±0.12) and (6.67±0.08) mg/mL, respectively. The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were (19.97±0.12)% and (6.65±0.08)%, respectively. (2) In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area, and could penetrate and diffuse to deeper parts of the skin. (3) MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells. The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells. The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety. (4) In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells, and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone. These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity, reduce melanin synthesis, and enhance the anti-skin pigmentation effect of tranexamic acid.

Key words: tranexamic acid, functionalized self-assembled micelles, skin pigmentation, in vitro transdermal, engineered skin material