针对骨的基于ZIF-8的纳米颗粒装载着万科米辛,用于治疗MRSA诱导的围假肢关节感染
Shuailong Liang1, Yixiao Pan2, Jiahao Wang3
1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
概括
新的纳米颗粒装满了万科米和龙酸有效地治疗了耐美西林的金黄色葡萄球菌 (Staphylococcus aureus) 周围假肢关节感染. 这种针对性,pH响应的药物输送系统显示出显著的抗菌活性,并减少了与感染相关的骨损伤.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 传染性疾病 传染性疾病
背景情况:
- 由甲素耐药黄金葡萄球菌 (MRSA) 引起的周围假肢关节感染 (PJI) 是由于抗菌素耐药性增加而造成的重大全球健康挑战.
- 传统抗生素对MRSA-PJI的疗效正在下降,需要新的治疗策略和药物输送系统.
研究的目的:
- 开发和评价含范素 (Van) 和化酸 (ZOL) 修饰的化物伊米达酸框架-8 (ZIF-8) 纳米颗粒 (VZZ-8 NPs) 用于针对性治疗MRSA诱导的PJI.
- 在体外和体内研究VZZ-8NP的骨定位能力,pH响应性药物释放,协同抗菌作用和治疗疗效.
主要方法:
- 制造ZIF-8纳米颗粒与万科米辛一起加载,并与龙酸 (VZZ-8NP) 进行修改.
- 在生理和酸性pH下评估VZZ-8NP的稳定性,pH反应性降解和药物释放动力学.
- 在体外评估抗菌活性对MRSA和生物膜形成的抑制.
- 使用MRSA诱导PJI的小鼠模型进行体内研究,以评估治疗疗效,抗炎作用和预防骨解.
主要成果:
- 由于ZOL的修改,VZZ-8 NP表现出偏好的骨准,在感染部位积累.
- 在酸性微环境 (pH 5.0) 中,VZZ-8 NP的快速降解引发了Zn2+和Van.的随时联合释放.
- Zn2+和Van的协同抗菌作用显著增强了MRSA根除 (93.84 ± 7.38%) 并抑制了生物膜形成 (95.36 ± 0.13%).
- 在体内,VZZ-8 NPs有效治疗MRSA-PJI,抑制局部炎症标记物 (TNF-α,IL-6) 并预防骨质溶解.
结论:
- 工程VZZ-8NP为MRSA-PJI提供了一个有前途的治疗策略,结合了向输送和pH响应释放以提高疗效.
- 来自VZZ-8NP的有针对性输送和协同药物释放的双重作用提供了一种全面的方法来对抗MRSA诱导的骨感染.
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