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Efficacy and safety of alpha lipoic acid-capped silver nanoparticles for oral applications

机译：口服应用硫辛酸封端的银纳米颗粒的功效和安全性

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Silver nanoparticles (AgNPs) are widely studied for their broad-spectrum antimicrobial effects, and can be utilised readily in biomaterials, however the cellular safety of specific AgNP formulations should be profiled prior to clinical usage. This study determined the cytotoxic effect of small sized (6 nm) alpha lipoic acid capped-AgNPs on human gingival fibroblasts (HGF), as compared to ionic silver and clinical antiseptics. The metabolic pathway was investigated to determine the cellular effects on HGF cells. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) was established for a range of oral related bacteria. Results showed that cell viability decreased with increasing AgNP concentration, whereas lower concentrations of AgNPs, (≤5 μg ml ~(?1) ) caused a significant increase in cell proliferation at 24 and 72 hour time points. The cytotoxicity profile of AgNPs exhibited significantly lower concentrations, relative to the dose of clinical efficacy, when compared to clinical antiseptics. Caspase 3/7 was not significantly altered when HGF cells were treated with 0.225 μg ml ~(?1) AgNPs, indicating cell necrosis rather than apoptosis. Quantitative RT ~(2) -PCR detected an upregulation of genes associated with oxidative stress and the G2M cell cycle checkpoint at ≤4 hours, but expression levels returned to levels consistent with control cells at 24–96 hours. An MIC range of 2.5–12.5 μg ml ~(?1) (min. Escherichia coli , Streptococcus mutans , S. mitis ; max. Staphylococcus aureus ) was determined across the bacterial species tested and an MBC range of 5–100 μg ml ~(?1) (min. E. coli , max. S. mutans ). The antimicrobial profile was similar to that of AgNO _(3) which suggested that the antimicrobial effect may be influenced by free Ag ~(+) release. It was concluded that alpha lipoic acid capped AgNPs possess limited cytotoxic activity to HGF cells when compared to clinically utilised oral antiseptics, observed via the cellular recovery after initial AgNP treatment and a lack of cumulative cytotoxic effect, whilst maintaining a broad range antimicrobial effect of the AgNPs.
机译：银纳米颗粒（AgNPs）具有广谱抗菌作用，因此得到了广泛的研究，可以很容易地用于生物材料中，但是特定AgNP制剂的细胞安全性应在临床使用之前进行分析。这项研究确定了与离子银和临床杀菌剂相比，小尺寸（6纳米）α硫辛酸加帽的AgNP对人牙龈成纤维细胞（HGF）的细胞毒性作用。研究了代谢途径以确定对HGF细胞的细胞作用。一系列口腔相关细菌的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）已确定。结果表明，随着AgNP浓度的增加，细胞活力降低，而较低浓度的AgNPs（≤5μgml〜（？1））则在24和72小时的时间点引起细胞增殖的显着增加。与临床防腐剂相比，相对于临床疗效剂量，AgNPs的细胞毒性谱显示出明显较低的浓度。当用0.225μgml〜（？1）AgNPs处理HGF细胞时，Caspase 3/7没有明显改变，表明细胞坏死而不是凋亡。定量RT〜（2）-PCR检测到≤4小时的氧化应激和G2M细胞周期检查点相关基因的上调，但在24-96小时时表达水平恢复到与对照细胞一致的水平。测定的整个细菌种类的MIC范围为2.5–12.5μgml〜（？1）（最小大肠杆菌，变形链球菌，链球菌;最大金黄色葡萄球菌），MBC范围为5-100μgml〜 （？1）（最小大肠杆菌，最大变形链球菌）。抗菌特性与AgNO_（3）相似，这表明抗菌作用可能受游离Ag〜（+）释放的影响。结论是，与临床使用的口服抗菌剂相比，α硫辛酸封端的AgNP对HGF细胞具有有限的细胞毒活性，在最初的AgNP治疗后通过细胞恢复观察到，并且缺乏累积的细胞毒作用，同时保持了广泛的抗菌作用。 AgNPs。

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