Cationic amphiphilic molecules as novel sclerosants for venous malformation treatment: A study on tranexamic acid-derived low-molecular-weight gels

• Published in: Biochemical and biophysical research communications 2024-11, Vol.735, p.150838, Article 150838
• Main Authors: Chen, Yongfeng, Song, Di, Hou, Qianqian, Ma, Mengrui, Zhao, Xiaoyun, Yang, Tianzhi, Xie, Huichao, Ding, Pingtian
• Format: Article
• Language: English
• Subjects: Animals; Cationic amphiphilic gelator; Cations - chemistry; Fatty Alcohols - chemistry; Fatty Alcohols - pharmacology; Fatty Alcohols - therapeutic use; Gels - chemistry; Humans; Low-molecular-weight gels; Male; Mice; Molecular Weight; Sclerosing Solutions - chemistry; Sclerosing Solutions - therapeutic use; Sclerotherapy; Sclerotherapy - methods; Self-delivery system; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; Surface-Active Agents - therapeutic use; Tranexamic acid; Tranexamic Acid - pharmacology; Tranexamic Acid - therapeutic use; Vascular Malformations - drug therapy; Vascular Malformations - pathology; Vascular Malformations - therapy; Veins - abnormalities; Veins - drug effects; Venous malformation
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150838

Venous malformation (VM) is a prevalent congenital vascular anomaly characterized by abnormal blood vessel growth, leading to disfigurement and dysfunction. Sclerotherapy, a minimally invasive approach, has become a primary therapeutic modality for VM, but its efficacy is hampered by the rapid dilution and potential adverse effects. In this study, we introduced a series of cationic amphiphilic molecules, fatty alcohol esters (TA6, TA8, and TA9) of tranexamic acid (TA), which self-assembled into low-molecular-weight gels (LMWGs) in water. The TA9, in particular, is released slowly when hydrogel is injected into the vein locally. Then, it damages the venous wall by destroying cell membranes and precipitating proteins, causing inflammation and thrombosis, thickening of the venous wall, effectively inducing irreversible vein fibrosis. Additionally, TA9 can be rapidly degraded into TA in plasma to reduce toxicity caused by diffusion. Overall, this study suggests that the cationic amphiphilic molecule TA9 is a promising sclerosant for VM treatment, offering a novel, effective, and safe therapeutic option with potential for clinical translation. [Display omitted] •A cationic surfactant sclerosant that can be self-assembled into hydrogels.•Vascular fibrosis is caused by the destruction of vascular wall and thrombosis.•Sclerosant can be degraded to improve biocompatibility.