[论文解读] Susceptibility of Methicillin Resistant Staphylococcus aureus to Vancomycin using Liposomal Drug Delivery System

Kiran Vishwasrao, Arjumanara Surti+1 more|arXiv (Cornell University)|Jan 15, 2018

Antimicrobial Resistance in Staphylococcus参考文献 20被引用 3

一句话总结

本研究探讨了万古霉素脂质体包封技术，以增强其对耐甲氧西林金黄色葡萄球菌（MRSA）的疗效。与游离万古霉素相比，脂质体递送系统使万古霉素的最低抑菌浓度（MIC）显著降低约50%，表现出更强的抗菌活性和增强的吞噬细胞清除能力，从而为克服MRSA中万古霉素耐药性提供了有前景的策略。

ABSTRACT

Staphylococcus aureus responsible for nosocomial infections is a significant threat to the public health. The increasing resistance of S.aureus to various antibiotics has drawn it to a prime focus for research on designing an appropriate drug delivery system. Emergence of Methicillin Resistant Staphylococcus aureus (MRSA) in 1961, necessitated the use of vancomycin "the drug of last resort" to treat these infections. Unfortunately, S.aureus has already started gaining resistances to vancomycin. Liposome encapsulation of drugs have been earlier shown to provide an efficient method of microbial inhibition in many cases. We have studied the effect of liposome encapsulated vancomycin on MRSA and evaluated the antibacterial activity of the liposome-entrapped drug in comparison to that of the free drug based on the minimum inhibitory concentration (MIC) of the drug. The MIC for liposomal vancomycin was found to be about half of that of free vancomycin. The growth response of MRSA showed that the liposomal vancomycin induced the culture to go into bacteriostatic state and phagocytic killing was enhanced. Administration of the antibiotic encapsulated in liposome thus was shown to greatly improve the drug delivery as well as the drug resistance caused by MRSA.

研究动机与目标

• 为应对万古霉素耐药性在MRSA中的日益增长的挑战，MRSA是医院感染的主要原因。
• 评估脂质体药物递送是否能提高万古霉素对MRSA的疗效。
• 比较脂质体包封万古霉素与游离万古霉素的最低抑菌浓度（MIC）。
• 评估脂质体万古霉素对细菌生长动力学和吞噬杀伤的影响。
• 开发一种靶向递送系统，以增强药物递送并克服MRSA中的耐药机制。

提出的方法

• 采用标准的薄膜水化法和挤出技术制备脂质体以包封万古霉素。
• 通过肉汤微量稀释法评估脂质体万古霉素的抗菌活性，以确定最低抑菌浓度（MIC）。
• 监测游离万古霉素与脂质体万古霉素存在下MRSA培养物的生长动力学，以评估其抑菌作用。
• 进行吞噬杀伤实验，比较巨噬细胞介导的清除作用中，MRSA对脂质体万古霉素与游离万古霉素的敏感性差异。
• 脂质体系统旨在提高药物稳定性、靶向递送能力及在细菌细胞内的渗透能力。
• 对数据进行分析，比较两种制剂的MIC值、生长抑制率及吞噬细胞清除速率。

实验结果

研究问题

• RQ1 与游离万古霉素相比，万古霉素的脂质体包封是否能降低其对MRSA的最低抑菌浓度（MIC）？
• RQ2 脂质体万古霉素如何影响MRSA培养物的生长阶段和存活率？
• RQ3 脂质体万古霉素在多大程度上增强了免疫细胞对MRSA的吞噬清除能力？
• RQ4 脂质体递送能否改善万古霉素在耐药性金黄色葡萄球菌株中的治疗指数？
• RQ5 脂质体万古霉素在增强抗菌疗效方面，其作用机制如何超越游离药物递送？

主要发现

• 脂质体万古霉素对MRSA的最低抑菌浓度（MIC）比游离万古霉素低约50%。
• 脂质体万古霉素使MRSA培养物进入抑菌状态，表明其具有有效的生长抑制作用。
• 与游离万古霉素相比，暴露于脂质体万古霉素的MRSA在吞噬杀伤中显著增强。
• 脂质体递送系统提高了药物递送效率，使在较低浓度下产生更强的抗菌活性。
• 脂质体包封的万古霉素在克服MRSA耐药机制方面表现出更优的疗效。
• 本研究证实，脂质体制剂可增强万古霉素对多重耐药性金黄色葡萄球菌的活性。