Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials.

Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials.
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DOI:
10.1186/s11671-018-2520-7
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发表时间:
2018-04-19
影响因子:
--
通讯作者:
Powell J
Powell J
中科院分区:
材料科学3区
文献类型:
--
作者:
Bastos CAP;Faria N;Ivask A;Bondarenko OM;Kahru A;Powell J

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细菌对抗菌剂治疗的耐药性是一个日益严重的临床问题。这对于局部应用和全身治疗都是如此。局部而言,铜离子可能是有效且廉价的抗菌剂,其通过多种途径起作用,从而限制细菌产生耐药性的机会。然而,铜的化学性质不适合于在生物相容的pH下容易释放铜离子的简易制剂。在这里,我们已经开发了纳米颗粒己二酸酒石酸氢氧化铜(CHAT)作为一种廉价,安全,易于合成的材料,应该能够在感染的伤口环境中释放抗菌铜离子。首先,我们合成了CHAT,并表明其分散的水合颗粒尺寸为2-5 nm,平均zeta电位为− 40 mV。接下来,当稀释到细菌培养基中时,CHAT表现出与氯化铜对大肠杆菌和金黄色葡萄球菌相似的功效,其中铜的剂量依赖性活性主要发生在12.5-50 mg/L左右。事实上,在这些水平下,CHAT非常迅速地溶解,并且如细菌铜生物传感器所证实的,显示出与来自氯化铜的铜离子相同的细胞内负载。然而,当以250 mg/L配制在局部施用的基质(即羟乙基纤维素)中时,CHAT优于氯化铜的益处是明显的。前者在杀菌范围内可快速缓释铜,而氯化铜在此浓度和pH下形成不溶性沉淀,24 h时释放量最大,为10 ± 7 mg/L。我们提供了一种实用的局部铜基抗菌治疗配方。值得进一步研究,特别是在体内。本文的在线版本(10.1186/s11671-018-2520-7)包含补充材料,可供授权用户使用。
Bacterial resistance to antimicrobial therapies is an increasing clinical problem. This is as true for topical applications as it is for systemic therapy. Topically, copper ions may be effective and cheap antimicrobials that act through multiple pathways thereby limiting opportunities to bacteria for resistance. However, the chemistry of copper does not lend itself to facile formulations that will readily release copper ions at biologically compatible pHs. Here, we have developed nanoparticulate copper hydroxide adipate tartrate (CHAT) as a cheap, safe, and readily synthesised material that should enable antimicrobial copper ion release in an infected wound environment. First, we synthesised CHAT and showed that this had disperse aquated particle sizes of 2–5 nm and a mean zeta potential of − 40 mV. Next, when diluted into bacterial medium, CHAT demonstrated similar efficacy to copper chloride against Escherichia coli and Staphylococcus aureus, with dose-dependent activity occurring mostly around 12.5–50 mg/L of copper. Indeed, at these levels, CHAT very rapidly dissolved and, as confirmed by a bacterial copper biosensor, showed identical intracellular loading to copper ions derived from copper chloride. However, when formulated at 250 mg/L in a topically applied matrix, namely hydroxyethyl cellulose, the benefit of CHAT over copper chloride was apparent. The former yielded rapid sustained release of copper within the bactericidal range, but the copper chloride, which formed insoluble precipitates at such concentration and pH, achieved a maximum release of 10 ± 7 mg/L copper by 24 h. We provide a practical formulation for topical copper-based antimicrobial therapy. Further studies, especially in vivo, are merited. The online version of this article (10.1186/s11671-018-2520-7) contains supplementary material, which is available to authorized users.
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