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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.

SUBMITTER: Ai XY

PROVIDER: S-EPMC5327358 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action.

Ai Xiao-Yu XY Liu Hui-Juan HJ Lu Cheng C Liang Cai-Li CL Sun Yan Y Chen Shuang S Sun Bo B Li Yang Y Liu Yan-Rong YR Zhang Qiang Q Liu Xue-Qiang XQ Xiao Ting T Jing Xue-Shuang XS Sun Tao T Zhou Hong-Gang HG Yang Cheng C

Theranostics 20170105 2

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 enric ...[more]

PMID: 28255340

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Project description:A rapid wound healing is beneficial for not only recovering esthetics but also reducing pain, complications and healthcare burdens. For such a purpose, continuous efforts have been taken to develop viable dressing material. Acellular dermal matrix (ADM) paste has been used to repair burn wounds and is shown to promote angiogenesis as well as fibroblast attachment and migration. However, its efficacy still needs to be significantly improved to meet clinical demands for accelerating acute skin wound healing. To approach this problem, we studied the added value of a human salivary peptide - Histatin 1 (Hst1). Hst1 was chosen because of its potency to promote the adhesion, spreading, migration, metabolic activity and cell-cell junction of major skin cells and endothelial cells. In this study, we hypothesized that ADM paste and Hst1 showed a better effect on the healing of surgically created acute skin wounds in mice since ADM paste may act as a slow release system for Hst1. Our results showed that the healing efficacy of 10 ?M topically administrated Hst1 was significantly higher compared to the control (no Hst1, no ADM) from day 3 to day 10 post-surgery. In contrast, ADM alone failed in our system at all time points. Also, the combination of ADM paste and Hst1 did not show a better effect on percentage of wound healing. Histological analysis showed that 10 ?M Hst1 was associated with maximal thickness of newly formed epidermal layer on day 7 as well as the largest collagen area on day 14. In addition, immunohistochemical staining showed that the number of CD31-positive blood vessels in the group of 10 ?M Hst1 was 2.3 times compared to the control. The vascular endothelial growth factor (VEGF) expression in the groups of 10 ?M Hst1 group and ADM + 10 ?M Hst1 group was significantly higher compared with the control group. Furthermore, 10 ?M Hst1 group was associated with significantly lower levels of CD68-positive macrophage number, interleukin-1? (IL-1?) expression and C-reactive protein (CRP) expression than those of the other groups (control, ADM alone and ADM + 10 ?M Hst1). In contrast, ADM was only associated with significantly lower CD68-positive macrophage number and IL-1? expression in comparison with the control. The co-administration of Hst1 and ADM paste did not yield more beneficial effects than Hst1 alone. In conclusion, the topically administrated of 10 ?M Hst1 could be a promising alternative dressing in managing acute wound healing.

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Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action.

Publications

Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action.

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