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Phenytoin quaternary ammonium salt is a novel wound treatment drug with both pro-healing and antibacterial effects.

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Title: Phenytoin quaternary ammonium salt is a novel wound treatment drug with both pro-healing and antibacterial effects.
Authors: Li, Yuchen1,2,3 (AUTHOR), Cui, Jiaming1,4 (AUTHOR), Zhou, Peihui1,5 (AUTHOR), Cao, Bixuan6 (AUTHOR), Zhao, Li7 (AUTHOR), Kong, Weize1 (AUTHOR), Sun, Xueheng7 (AUTHOR), Fang, Ya3 (AUTHOR), Wang, Jinwu1,3 (AUTHOR) wangjw@sjtu.edu.cn, Song, Mingzhi1 (AUTHOR) songmingzhi@sjtu.edu.cn, Wang, Li1,5 (AUTHOR) wlyjy73122@126.com
Source: Chemical Engineering Journal. Dec2025, Vol. 526, pN.PAG-N.PAG. 1p.
Subjects: Wound healing, Antibacterial agents, Cell proliferation, Quaternary ammonium salts, Neovascularization, Phenytoin, Wnt genes
Abstract: Bacterial infection and impaired regeneration are main factors leading to wound healing disorder. Current treatments offer uncertain efficacy. Repurposing old drugs is a promising strategy for wound treatment. Phenytoin sodium (PS) has been shown to accelerate wound healing besides the classical antiepileptic effect. Unfortunately, the low solubility and no antibacterial effect limit its widespread use. Quaternary ammonium salts are able to provide the ideal groups for compound modification. This study aimed to synthesize a new compound for both antibacterial and regeneration promotion effects. Phenytoin quaternary ammonium salt (Pn-NH 4) was synthesized from PS via ion-exchange resin reaction with tetrabutylammonium hydroxide. The newly developed compound was then incorporated with gelatin methacryloyl (GelMA) to fabricate a novel wound dressing. In vitro studies demonstrated that the newly developed Pn-NH 4 significantly enhances cell proliferation and stimulates angiogenesis. Pn-NH 4 demonstrates strong broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative strains at 25 μg/mL. Transcriptomic sequencing and molecular docking were employed, revealing that Pn-NH 4 may promote wound healing by activating the WNT pathway. Furthermore, in vivo experiments demonstrated that this novel wound dressing promotes angiogenesis, accelerates re-epithelialization and collagen deposition, ultimately enhancing wound healing. This new compound is expected to provide a new option for wound treatment. • Pn-NH 4 was successfully synthesized from phenytoin sodium via ion-exchange resin reaction with tetrabutylammonium hydroxide. • Pn-NH 4 has antibacterial and regeneration promotion effects. • Pn-NH 4 may promote wound healing by activating the WNT pathway. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
Abstract:Bacterial infection and impaired regeneration are main factors leading to wound healing disorder. Current treatments offer uncertain efficacy. Repurposing old drugs is a promising strategy for wound treatment. Phenytoin sodium (PS) has been shown to accelerate wound healing besides the classical antiepileptic effect. Unfortunately, the low solubility and no antibacterial effect limit its widespread use. Quaternary ammonium salts are able to provide the ideal groups for compound modification. This study aimed to synthesize a new compound for both antibacterial and regeneration promotion effects. Phenytoin quaternary ammonium salt (Pn-NH 4) was synthesized from PS via ion-exchange resin reaction with tetrabutylammonium hydroxide. The newly developed compound was then incorporated with gelatin methacryloyl (GelMA) to fabricate a novel wound dressing. In vitro studies demonstrated that the newly developed Pn-NH 4 significantly enhances cell proliferation and stimulates angiogenesis. Pn-NH 4 demonstrates strong broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative strains at 25 μg/mL. Transcriptomic sequencing and molecular docking were employed, revealing that Pn-NH 4 may promote wound healing by activating the WNT pathway. Furthermore, in vivo experiments demonstrated that this novel wound dressing promotes angiogenesis, accelerates re-epithelialization and collagen deposition, ultimately enhancing wound healing. This new compound is expected to provide a new option for wound treatment. • Pn-NH 4 was successfully synthesized from phenytoin sodium via ion-exchange resin reaction with tetrabutylammonium hydroxide. • Pn-NH 4 has antibacterial and regeneration promotion effects. • Pn-NH 4 may promote wound healing by activating the WNT pathway. [ABSTRACT FROM AUTHOR]
ISSN:13858947
DOI:10.1016/j.cej.2025.170734