Abstract：
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 ≈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.
摘要：
全身使用氨甲环酸（TA）作为口服药物可能会带来不良反应，而皮内注射导致疼痛和感染的风险。此外，高亲水性TA难以穿透含有大量疏水性脂质化合物的皮肤屏障，这对其局部应用构成了巨大的限制。目前的经皮TA给药策略，患有低药物负荷率，加上它的合成复杂性，时间消耗等。,增加了TA在临床治疗中局部应用的难度。为了增加TA的渗透率，开发了一种使用TA加载的ZIF-8(TA@ZIF-8)的新方法。理论模拟表明，通过TA的物理吸附和化学键合，TA@ZIF-8的包封率达到近25％，并且通过激活水通道蛋白3（AQP-3）蛋白提高了TA的渗透性。此外,体内和体外实验证明了TA@ZIF-8的穿透性和细胞内摄取的优势,轻微的细胞毒性，和抑制黑色素生成和炎症因子。此外，临床试验证明了TA@ZIF-8治疗黄褐斑和酒渣鼻的安全性和有效性.这项工作提出了TA的潜在局部应用，没有与全身用药相关的安全性问题。本文受版权保护。保留所有权利。
