克拉霉素脂质体的制备及体内外抗菌评价

doi:10.5246/jcps.2018.06.041

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (6): 408-414.DOI: 10.5246/jcps.2018.06.041

克拉霉素脂质体的制备及体内外抗菌评价

张文茜, 彭光华, 宋茂远, 王佳星, 殷梦雅, 李佳佳, 刘雅婕, 张媛媛, 李馨儒^*

北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室, 北京 100191

收稿日期:2018-03-16 修回日期:2018-04-14 出版日期:2018-06-30 发布日期:2018-05-18
通讯作者: Tel.: +86-010-82801508, E-mail: ll@bjmu.edu.cn
基金资助:
The National Natural Science Foundation of China (Grant No. 81202488).

Preparation and evaluation of liposomal clarithromycin with antimicrobial effect

Wenxi Zhang, Guanghua Peng, Maoyuan Song, Jiaxing Wang, Mengya Yin, Jiajia Li, Yajie Liu, Yuanyuan Zhang, Xinru Li^*

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System; School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2018-03-16 Revised:2018-04-14 Online:2018-06-30 Published:2018-05-18
Contact: Tel.: +86-010-82801508, E-mail: ll@bjmu.edu.cn
Supported by:
The National Natural Science Foundation of China (Grant No. 81202488).

摘要/Abstract

摘要：

本研究的目的在于制备由Tat肽和麦胚凝集素修饰(WGA)修饰的脂质体递送系统, 有效发挥抗菌效应。分别对其理化性质、耐甲氧西林金黄色葡萄球菌(MRSA)的最低抑菌浓度(MIC)、杀菌动力学、细胞摄取、生物膜形成抑制以及体内抗菌效果进行评价。研究结果表明, 由Tat和WGA双修饰的载克拉霉素脂质体具有最低的MIC值和杀菌曲线, 流式细胞实验结果表明双修饰的脂质体可将更多的香豆素6导入细菌内部。此外, 该脂质体还能有效抑制MRSA生物膜的形成。体内实验结果表明, 经过双修饰脂质体给药, 小鼠脓肿部位的MRSA菌落数显著低于其他组(P<0.01), 即具有最强的体内抗菌效果。总之, 由Tat和WGA修饰的脂质体递送系统希望称为有效的抗耐药菌感染的策略。

关键词: 耐甲氧西林金黄色葡萄球菌, 抗菌, 脂质体, 克拉霉素, 生物膜

Abstract:

In this study, we developed a novel liposomal delivery system modified by Tat peptide and wheat germ agglutinin (WGA) with antimicrobial effect. Physicochemical parameters, in vitro antimicrobial, time-kill study, cellular uptake, biofilm formation inhibition and in vivo antibacterial efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Minimum inhibitory concentrations (MICs) and colony-forming units (CFUs) in the time-kill study for Tat-WGA-modified liposomal clarithromycin (CLA-TatWGALip) were lower than those of free and other modified liposomal CLA. Flow cytometry analysis disclosed that TatWGALip delivered more coumarin 6 into bacteria. Furthermore, Tat-WGA-modified liposomal CLA efficiently inhibited the formation of MRSA biofiom. CFU of MRSA in the abscess of mice treated with CLA-TatWGALip was significantly lower than that of any others (P<0.01). Collectively, liposomal delivery system modified by Tat and WGA could be a promising anti-resistant infection strategy.

Key words: Methicillin-resistant Staphylococcus aureus, Antimicrobial, Liposomes, Clarithromycin, Biofilm

中图分类号:

R944

Supporting:

张文茜, 彭光华, 宋茂远, 王佳星, 殷梦雅, 李佳佳, 刘雅婕, 张媛媛, 李馨儒. 克拉霉素脂质体的制备及体内外抗菌评价[J]. 中国药学(英文版), 2018, 27(6): 408-414.

Wenxi Zhang, Guanghua Peng, Maoyuan Song, Jiaxing Wang, Mengya Yin, Jiajia Li, Yajie Liu, Yuanyuan Zhang, Xinru Li. Preparation and evaluation of liposomal clarithromycin with antimicrobial effect[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(6): 408-414.

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克拉霉素脂质体的制备及体内外抗菌评价

Preparation and evaluation of liposomal clarithromycin with antimicrobial effect

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