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在 50°C 的热疗辅助下 5 分钟,提高低剂量庆大霉素的抗菌疗效。

Enhancing the antibacterial efficacy of low-dose gentamicin with 5 minute assistance of photothermy at 50 °C.

机构信息

Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan 430062, China.

出版信息

Biomater Sci. 2019 Mar 26;7(4):1437-1447. doi: 10.1039/c8bm01539b.

DOI:10.1039/c8bm01539b
PMID:30666993
Abstract

Implant materials are prone to bacterial infections and cause serious consequences, while traditional antibiotic therapy has a long treatment cycle and even causes bacterial resistance. In this work, a photothermal therapy (PTT) assisted drug release system has been developed on the implant surface for in situ rapid disinfection under 808 nm light irradiation within a short time, in which gentamicin (Gent) is loaded by polyethylene glycol (PEG) modified molybdenum disulfide (MoS2) on Ti surface, and then encapsulated with chitosan (CS) (CS/Gent/PEG/MoS2-Ti). The hyperthermia produced by the coatings irradiated by 808 nm near-infrared (NIR) light can not only accelerate the local release of Gent, but also reduce the activity of bacteria, which makes it easy for these locally released drugs to enter the interior of the bacteria to inhibit the protein synthesis and destroy the cell membrane. When maintained at 50 °C for 5 min under NIR irradiation, this system can achieve an antibacterial efficacy of 99.93% and 99.19% against Escherichia coli and Staphylococcus aureus, respectively. By contrast, even after treatment for 120 min, only a 93.79% antibacterial ratio can be obtained for Gent alone. This is because hyperthermia produced from the coatings during irradiation can assist antibiotics in killing bacteria in a short time. Even under a low dose of 2 μg mL-1, the photothermal effect assisted gentamicin can achieve an antibacterial efficacy of 96.86% within 5 min. In vitro cell culture shows that the modified surface can facilitate cell adhesion, spreading and proliferation. The 7 day subcutaneous infection model confirms that the prepared surface system can exhibit a much faster sterilization and tissue reconstruction than the control group with light assistance. Compared with the traditional drug release system, this photothermy controlled drug-loaded implant surface system can not only provide rapid and high-efficiency in situ sterilization, but also offer long-term prevention of local bacterial infection.

摘要

植入物材料容易受到细菌感染,导致严重后果,而传统的抗生素治疗具有较长的治疗周期,甚至会导致细菌耐药性。在这项工作中,在植入物表面开发了一种光热疗法(PTT)辅助药物释放系统,可在 808nm 光照射下在短时间内在原位快速消毒,其中庆大霉素(Gent)通过聚乙二醇(PEG)修饰的二硫化钼(MoS2)负载在 Ti 表面上,然后用壳聚糖(CS)(CS/Gent/PEG/MoS2-Ti)封装。涂层在 808nm 近红外(NIR)光照射下产生的热疗不仅可以加速 Gent 的局部释放,还可以降低细菌的活性,使这些局部释放的药物更容易进入细菌内部,抑制蛋白质合成并破坏细胞膜。当在 NIR 照射下保持 5min 时,该系统对大肠杆菌和金黄色葡萄球菌的抗菌效率分别达到 99.93%和 99.19%。相比之下,即使 Gent 单独治疗 120min,也只能获得 93.79%的抗菌率。这是因为照射时涂层产生的热疗可以在短时间内辅助抗生素杀死细菌。即使在低剂量 2μg mL-1 下,光热效应辅助庆大霉素也可以在 5min 内实现 96.86%的抗菌效果。体外细胞培养表明,改性表面可以促进细胞的黏附、铺展和增殖。7 天的皮下感染模型证实,与对照组相比,制备的表面系统在光照辅助下可以更快地实现灭菌和组织重建。与传统的药物释放系统相比,这种光热控制的载药植入物表面系统不仅可以提供快速高效的原位灭菌,还可以提供长期预防局部细菌感染。

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