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载银万古霉素修饰介孔硅抗菌活性对耐甲氧西林金黄色葡萄球菌

Antibacterial activity of a silver-incorporated vancomycin-modified mesoporous silica against methicillin-resistant .

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Polymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Tehran, Iran.

出版信息

J Biomater Appl. 2024 Nov;39(5):439-454. doi: 10.1177/08853282241274517. Epub 2024 Aug 28.

Abstract

Since conventional antibiotics are almost ineffective on methicillin-resistant (MRSA) strains, designing their antibacterial alternatives is necessary. Besides, the use of vancomycin is applied for specific detection of the bacteria. Silver-incorporated vancomycin-modified mesoporous silica nanoparticles (MSNs@Van@Ag NPs) were designed for detection and treatment of MRSA bacteria. Mesoporous silica nanoparticles (MSNs) were synthesized through the template method, modified with vancomycin, and finally incorporated with silver nanoparticles (Ag NPs). The MSNs@Van@Ag NPs with a homogenously spherical shape, average size of 50-100 nm, surface area of 955.8 m/g, and thermal stability up to 200°C were successfully characterized. The amount of Ag incorporated into the MSNs@Van@Ag was calculated at 3.9 ppm and the release amount of Ag was received at 2.92 ppm (75%) after 100 h. The in vitro antibacterial susceptibility test showed the MIC of 100 μg mL for MSNs@Van and 50 μg mL for MSNs@Van@Ag, showing in vitro enhanced effect of Ag and vancomycin in the bactericidal process. An in vivo acute pneumonia model was performed and biochemical assays and pathological studies confirmed the nanomedicine's short-term safety for in vivo application. Cytokine assay using ELISA showed that MSN@Van@Ag causes a reduction of pro-inflammatory cytokines and bacterial proliferation leading to alleviation of inflammatory response.

摘要

由于传统抗生素对耐甲氧西林金黄色葡萄球菌(MRSA)菌株几乎无效,因此有必要设计它们的抗菌替代品。此外,万古霉素的使用可用于特定的细菌检测。设计载银万古霉素修饰的介孔硅纳米粒子(MSNs@Van@Ag NPs)用于检测和治疗耐甲氧西林金黄色葡萄球菌细菌。通过模板法合成介孔硅纳米粒子(MSNs),用万古霉素进行修饰,最后加入银纳米粒子(Ag NPs)。成功地对 MSNs@Van@Ag NPs 进行了均匀球形、平均尺寸为 50-100nm、比表面积为 955.8m/g 和热稳定性高达 200°C 的特征描述。计算出 MSNs@Van@Ag 中 Ag 的掺入量为 3.9ppm,在 100h 后,Ag 的释放量为 2.92ppm(75%)。体外抗菌药敏试验表明,MSNs@Van 的 MIC 为 100μg/mL,MSNs@Van@Ag 的 MIC 为 50μg/mL,表明 Ag 和万古霉素在杀菌过程中有体外增强作用。进行了体内急性肺炎模型,生物化学分析和病理研究证实了纳米药物在体内应用的短期安全性。ELISA 细胞因子测定表明,MSN@Van@Ag 可减少促炎细胞因子和细菌增殖,从而减轻炎症反应。

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