Bacterial infections represent one of the leading causes of mortality in the world. Among causative pathogens,Staphylococcus aureusis prominently known as the underlying cause of many multidrug resistant infections that are often treated with the first-line choice antibiotic vancomycin (VCM). Loading antibiotics into polymeric nanoparticles (Np) displays promise as an alternative method to deliver therapy due to the greater access and accumulation of the antibiotic at the site of the infection as well as reducing toxicity, irritation and degradation. The aim of this work was to prepare, characterize and evaluate VCM-loaded nanoparticles (VNp) for use againstS. aureusstrains. Moreover, conjugation of Nps with holo-transferrin (h-Tf) was investigated as an approach for improving targeted drug delivery. VNp were prepared by double emulsion solvent evaporation method using PLGA and PVA or DMAB as surfactants. The particles were characterized for size distribution, Zeta Potential, morphology by transmission electron microscopy, encapsulation yield and protein conjugation efficiency. Process yield and drug loading were also investigated along with anin vitroevaluation of VNp antimicrobial effects againstS. aureusstrains. Results showed that Np were spontaneously formed with a mean diameter lower than 300 nm in a narrow size distribution that presented a spherical shape. The bioconjugation with h-Tf did not appear to increase the antimicrobial effect of VNp. However, non-bioconjugated Np presented a minimal inhibitory concentration lower than free VCM against a MRSA (Methicillin-resistantS. aureus) strain, and slightly higher against a VISA (VCM intermediateS. aureus) strain. VNp without h-Tf showed potential to assist in the development of new therapies againstS. aureusinfections.

中文翻译：

---

抗万古霉素中间体和耐甲氧西林金黄色葡萄球菌菌株的万古霉素纳米颗粒

细菌感染是世界上导致死亡的主要原因之一。在致病病原体中，金黄色葡萄球菌是许多耐多药感染的主要病因，通常使用一线抗生素万古霉素 (VCM) 进行治疗。将抗生素装入聚合物纳米粒子 (Np) 中显示出作为提供治疗的替代方法的前景，因为抗生素在感染部位的接触和积累更多，并且可以减少毒性、刺激和降解。这项工作的目的是制备、表征和评估负载 VCM 的纳米粒子 (VNp) 以用于对抗 S。金黄色葡萄球菌。此外，研究了将 Nps 与全转铁蛋白 (h-Tf) 结合作为改善靶向药物递送的方法。以PLGA和PVA或DMAB为表面活性剂，采用双乳液溶剂蒸发法制备VNp。对颗粒的尺寸分布、Zeta 电位、通过透射电子显微镜的形态、包封产率和蛋白质缀合效率进行表征。还研究了工艺收率和载药量以及 VNp 对 S 的抗菌作用的体外评估。金黄色葡萄球菌。结果表明，Np 是自发形成的，平均直径小于 300 nm，呈球形，呈窄尺寸分布。与 h-Tf 的生物偶联似乎没有增加 VNp 的抗菌作用。然而，非生物共轭 Np 对 MRSA（耐甲氧西林金黄色葡萄球菌）菌株的最小抑制浓度低于游离 VCM，对 VISA（VCM 中间体金黄色葡萄球菌）菌株略高。不含 h-Tf 的 VNp 显示出有助于开发新疗法的潜力。金黄色葡萄球菌感染。