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 could 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 its 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) was developed. The encapsulation efficiency of TA@ZIF-8 reached nearly 25% through physical adsorption and chemical bonding of TA indicated by theoretical simulation and the improved TA penetration was elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments have demonstrated 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 have demonstrated 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. This article is protected by copyright. All rights reserved.