title: Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action.
abstract: Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could accelerate dermal wound healing and strong inflammation control in Sprague-Dawley rats (SD rat) and Bama minipigs. Due to its low solubility, PnAg led to low toxicity and blood enrichment in animals. Furthermore, PnAg could upregulate the promoter activity of Jak, Stat3, and Stat3 downstream proteins. Therefore, PnAg may serve as an effective therapeutic compound for wound healing through regulating the gp130/Jak/Stat3 signaling pathway.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Ai
authors.affiliation: Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Cai-Li
authors.initials: CL
authors.lastname: Liang
authors.affiliation: Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Xue-Qiang
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Xue-Shuang
authors.initials: XS
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China;; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D050822:Cytokine Receptor gp130 / Q000819:agonists; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D053612:Janus Kinases / Q000378:metabolism; D049329:Nanostructures / Q000008:administration & dosage*; D010672:Phenytoin / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012834:Silver / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D000891:Anti-Infective Agents, Local; D007155:Immunologic Factors; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130; D012834:Silver; D010672:Phenytoin; D053612:Janus Kinases
keywords: Nanometer; Stat3.; inflammation; phenytoin; wound healing