Bacterial biofilms of Staphylococcus aureus, formed on implants, have a massive impact on the increasing number of antimicrobial resistance cases. The current treatment for biofilm-associated infections is based on the administration of antibiotics, failing to target the biofilm matrix. This work is focused on the development of multiple lipid nanoparticles (MLNs) encapsulating the antibiotic moxifloxacin (MOX). The nanoparticles were functionalized with d-amino acids to target the biofilm matrix. The produced formulations exhibited a mean hydrodynamic diameter below 300 nm, a low polydispersity index, and high encapsulation efficiency. The nanoparticles exhibited low cytotoxicity towards fibroblasts and low hemolytic activity. To target bacterial cells and the biofilm matrix, MOX-loaded MLNs were combined with a nanosystem encapsulating a matrix-disruptive agent: N-acetyl-L-cysteine (NAC). The nanosystems alone showed a significant reduction of both S. aureus biofilm viability and biomass, using the microtiter plate biofilm model. Further, biofilms grown inside polyurethane catheters were used to assess the effect of combining MOX-loaded and NAC-loaded nanosystems on biofilm viability. An increased antibiofilm efficacy was observed when combining the functionalized MOX-loaded MLNs and NAC-loaded nanosystems. Thus, nanosystems as carriers of bactericidal and matrix-disruptive agents are a promising combinatory strategy towards the eradication of S. aureus biofilms.

中文翻译：

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抗菌膜组合策略：装载莫西沙星的纳米系统和封装的 N-乙酰基-L-半胱氨酸

在植入物上形成的金黄色葡萄球菌细菌生物膜对越来越多的抗菌素耐药病例产生了巨大影响。目前对生物膜相关感染的治疗是基于抗生素的给药，未能针对生物膜基质。这项工作的重点是开发包封抗生素莫西沙星 (MOX) 的多种脂质纳米颗粒 (MLN)。纳米粒子被d功能化-靶向生物膜基质的氨基酸。所生产的制剂表现出低于 300 nm 的平均流体动力学直径、低多分散指数和高封装效率。纳米颗粒对成纤维细胞表现出低细胞毒性和低溶血活性。为了靶向细菌细胞和生物膜基质，载有 MOX 的 MLN 与封装基质破坏剂 N-乙酰基-L-半胱氨酸 (NAC) 的纳米系统相结合。仅纳米系统就显示金黄色葡萄球菌显着减少生物膜活力和生物量，使用微量滴定板生物膜模型。此外，在聚氨酯导管内生长的生物膜用于评估结合载有 MOX 和载有 NAC 的纳米系统对生物膜活力的影响。当结合功能化的载有 MOX 的 MLN 和载有 NAC 的纳米系统时，观察到抗生物膜功效增加。因此，作为杀菌剂和基质破坏剂载体的纳米系统是根除金黄色葡萄球菌生物膜的有前途的组合策略。