Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches approximate to 25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration. The present study encapsulates tranexamic acid (TA) into ZIF-8 (TA@ZIF-8) via the coprecipitation approach for enhanced transdermal delivery. The results demonstrate that TA@ZIF-8 penetrates the skin barrier to the dermis by activating the aquaporin-3 (AQP-3) and exhibits excellent properties in mitigating pigmentation and inflammation, which delivers a multidimensional therapy for melasma and rosacea. image