Enhanced Skin Permeation and Pigmentation Reduction Effects of a Novel Tranexamic Acid-Mandelic Acid Ion-Pairing Complex

Abstract

Purpose: This study investigated the enhanced skin permeation and pigmentation reduction effects of an ion-pair complex formed between tranexamic acid (TXA) and mandelic acid (MA). The TXA-MA complex demonstrated superior skin permeability and greater inhibition of cytokine expression compared to TXA alone, ultimately proving more effective in reducing skin pigmentation. Methods: After spectroscopic analysis of the TXA-MA ion-pairing complex (TXA-MA complex) structure, an in vitro skin permeation study was conducted using a Franz cell system with porcine skin. Additionally, the effect of the TXA-MA complex on UVB (ultraviolet B)-induced expression changes of inflammation-related genes (IL-1α, IL-6, IL-8, COX2) was evaluated using a human epidermal keratinocyte cell lines (HaCaT) cell model. Finally, an in vivo human study was performed to analyze the efficacy of TXA-MA in reducing actual skin pigmentation. Results: The formation of the TXA-MA complex was confirmed through zeta-potential measurements, 1H NMR study, and Fourier-transform infrared spectroscopy (FT-IR) spectroscopy. Skin permeation studies using porcine skin showed enhanced permeability of the TXA-MA complex compared to TXA at equivalent concentrations. In the HaCaT cell model, the TXA-MA complex exhibited greater inhibition of inflammatory markers IL-1α, IL-6, IL-8, and COX-2 expression than TXA alone. Finally, a 4-week human clinical study using ANTERA 3D imaging demonstrated that the TXA-MA complex was significantly more effective than TXA alone in reducing skin pigmentation. Conclusion: This study successfully formed a TXA-MA complex. Compared to TXA, the TXA-MA complex showed superior effects in skin permeability, inhibition of inflammatory marker expression, and actual skin pigmentation reduction. These results suggest that the TXA-MA complex holds greater potential as an effective cosmetic ingredient for pigmentation improvement than TXA alone.