Preparation and evaluation of lipid polymer nanoparticles for eradicating H-pylori biofilm and impairing antibacterial resistance in vitro
Preparation and evaluation of lipid polymer nanoparticles for eradicating H-pylori biofilm and impairing antibacterial resistance in vitro
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DOI：
10.1016/j.ijpharm.2015.09.055
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发表时间：
2015-11-30
影响因子：
5.8
通讯作者：
Wu, Chuanbin
中科院分区：
文献类型：
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作者：
Cai, Jie;Huang, Huizhi;Wu, Chuanbin
幽门螺杆菌对经典抗菌药物治疗的耐药性已变得越来越普遍，因此认为生物膜在耐药机制中起重要作用。本文以10.2%的阿莫西林（AMX）和一种新的抗H.制备了以鼠李糖脂和磷脂为外层混合脂质层的幽门粘附材料硫酸果胶（佩奇）脂质聚合物纳米粒（RHL-PC-LPN）。RHL-PC-LPN粒径约为200 nm，带负电荷，在24 h内持续完全释药。在一项体外研究中，H. pylori生物膜模型成功建立。RHL-PC-LPN对H. pylori在生物膜的形式。RHL-PC-LPN组、PC-LPN组和佩奇+ AMX组对H. pylori粘附于AGS细胞。探讨H. pylori的生物被膜形成的最低抑菌浓度（MIC）从125 μ g/ml降至15.6 μ g/ml。激光扫描共聚焦显微镜观察到RHL-PC-LPN组FITC-ConA标记的细胞外多聚物（EPS）减少。因此，我们得出结论，采用鼠李糖脂和磷脂的混合脂质作为纳米颗粒的外层和佩奇作为内核产生能够显著破坏H的系统。通过清除EPS以及抑制细菌的粘附和定殖来抑制pylori生物膜。(C)2015爱思唯尔B. V.保留所有权利。
The resistance of Helicobacter pylori to classical antimicrobial treatment has become increasingly common, whereupon biofilms are considered to play an important role in the resistance mechanism. Here 10.2% of amoxicillin (AMX) and a novel anti H. pylori adhesion material pectin sulfate (PECS) loaded lipid polymer nanoparticles (LPN) were prepared, with rhamnolipid and phospholipids as the outer mixed lipids layer (RHL-PC-LPN). The size of RHL-PC-LPN was around 200 nm, was negatively-charged, and showed sustained and complete drug release within 24 h. In an in vitro study, H. pylori biofilm models were successfully established. RHL-PC-LPN, superior to PC-LPN (employing phospholipids only as the outer lipid layer), PECS + AMX (mixture of PECS and AMX) and AMX only, was proven to significantly eradicate H. pylori in the biofilm form. In accordance to our previous results, the RHL-PC-LPN group, together with the PC-LPN and PECS + AMX group, inhibited H. pylori from adhering to AGS cells. Investigating the underlying mechanisms contributing to the death of H. pylori caused by RHL-PC-LPN, we found that LPN could lower the antibiotic minimal inhibition concentration (MIC) to biofilm form from 125 mu g/ml to 15.6 mu g/ml. Furthermore, FITC-ConA labeled extracellular polymeric substances (EPS) were decreased in the RHL-PC-LPN group observed by a laser scanning confocal microscope. Therefore, we conclude that employing the mixed lipids of rhamnolipid and phospholipids as the outer layer of nanoparticles and PECS as the inner core produces a system capable of significantly disrupting H. pylori biofilm by eliminating the EPS as well as inhibiting the adherence and colonization of bacteria. (C) 2015 Elsevier B.V. All rights reserved.