TiO2 纳米管阵列和负载抗生素对革兰氏阳性和革兰氏阴性细菌的协同抗菌活性和抑制作用

Emmanuel Einyat Opolot, Haochen Wang, J. Capadona, Horst A. von Recum, Hoda Amani Hamedani
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摘要

导言:植入式医疗器械仍然很容易受到细菌感染。抗生素耐药菌株的不断产生不仅加剧了这些感染,也使目前的治疗策略变得无能为力。现在比以往任何时候都更需要创新而有效的方法来对付耐药细菌。本研究探讨了二氧化钛纳米管阵列(TNAs)与生俱来的抗菌特性及其在体外局部递送抗生素灭活革兰氏阳性和阴性细菌的能力:方法:采用两步电化学阳极氧化工艺,在钛基底上生长直径为 100 纳米、长度为 5 微米的二氧化钛纳米管阵列:培养 24 小时后,制成的 TNA 对大肠杆菌的清除率为 100%,对金黄色葡萄球菌的清除率为 97%。根据 14 天的测量,负载抗生素的 TNA 可持续缓释头孢他啶和亚胺培南。体外细菌研究表明,负载头孢他啶和亚胺培南的 TNA 能够完全抑制肺炎克雷伯菌的生长,培养 24 和 48 小时后,肺炎克雷伯菌的清除率达到 100%。细菌抑制试验显示,与原装 TNA 相比,装载亚胺培南的 TNA 对肺炎克雷伯菌的抑制区明显扩大,相差 18 毫米,这种抑制区可维持 7 天,TNA 释放的抗生素剂量为 10 μgmL-1 左右,低于与抗菌 TNA 结合使用时彻底根除耐多药细菌所需的剂量。我们的研究结果凸显了 TNA 作为一种多功能平台的潜力,可用于解决与植入式医疗器械中细菌感染和抗生素耐药性有关的治疗策略。
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Synergistic antibacterial activity and inhibition of TiO2 nanotube arrays and loaded antibiotics against gram-positive and gram-negative bacteria
Introduction: Implantable medical devices continue to be vulnerable to bacterial infections. The unrelenting formation of antibiotic resistant bacterial strains not only exacerbates these infections but also renders the current treatment strategies impotent. The need is greater than ever for innovative and effective approaches to counteract drug-resistant bacteria. This study examines the innate antibacterial properties of TiO2 nanotube arrays (TNAs) and their ability to locally deliver antibiotics to inactivate gram-positive and gram-negative bacteria, in vitro.Methods: Using a two-step electrochemical anodization process, TNAs with a diameter of ∼100 nm and a length of ∼5 µm were grown on titanium substrates.Results and Discussion: After 24 h of incubation, as-fabricated TNAs showed 100% clearance of Escherichia coli, and 97% clearance of Staphylococcus aureus growth. The antibiotic-loaded TNAs demonstrated sustained slow-release of cefotaxime and imipenem measured over 14 days. In vitro bacterial studies revealed the capability of cefotaxime- and imipenem-loaded TNAs in completely inhibiting the growth with 100% clearance of Klebsiella pneumoniae after 24 and 48 h of incubation. Bacterial inhibition assay revealed a significantly enlarged inhibition zone difference of 18 mm around the imipenem-loaded TNAs against K. pneumoniae compared to the as-fabricated TNAs which was maintained for 7 days with ∼10 μgmL−1 of antibiotic released from the TNAs which was found to be lower than the dose required to completely eradicate multidrug resistant bacteria when used in conjunction with the antibacterial TNAs. The results of our study highlight the potential of TNAs as a versatile platform for addressing treatment strategies related to bacterial infections and antibiotic resistance in implantable medical devices.
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