Mucus penetration enhanced lipid polymer nanoparticles improve the eradication rate of Helicobacter pylori biofilm
Mucus penetration enhanced lipid polymer nanoparticles improve the eradication rate of Helicobacter pylori biofilm
复制标题
粘液渗透增强脂质聚合物纳米颗粒提高幽门螺杆菌生物膜的根除率
DOI：
10.1016/j.jconrel.2019.02.039
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发表时间：
2019-04-28
影响因子：
10.8
通讯作者：
Hu, Haiyan
中科院分区：
文献类型：
--
作者：
Li, Pengyu;Chen, Xiaonan;Hu, Haiyan
幽门螺杆菌（H. pylori）对常规抗生素治疗的依赖最近变得普遍。生物膜的形成与H.在过去的几十年里，此外，H.幽门螺杆菌在位于粘液层下的消化道上皮上定殖，这进一步降低了治疗功效，因为粘液层捕获并去除包括药物在内的外源物质。在此，我们报道了一种新的脂质聚合物纳米颗粒（LPNs），以克服生物膜和粘液层的阻塞。LPNs以壳聚糖纳米粒子（CS NPs）为核，以含有鼠李糖脂（RHL）的混合脂质层为壳，并进一步用DSPE-PEG 2000对LPNs表面进行改性以提高亲水性。克拉霉素（clarithromycin，简称克拉霉素）是治疗H。pylori感染，被封装在LPNs中。LPNs，特别是100%的RHL作为脂质壳的制剂，对H. pylori生物被膜的破坏主要表现在生物被膜的生物量和活力显著降低，生物被膜结构被破坏，胞外聚合物（EPS）被清除。LPNs的抗生物膜活性与以下因素有关：1）RHL对生物膜基质的破坏作用; 2）C5 NPs和CS NPs对生物膜细菌的抗菌作用; 3）CS NPs和RHL对细菌粘附和生物膜形成的抑制作用。此外，PEG化的LPNs可以快速穿透粘液而不与粘蛋白相互作用，并有效地清除H。粘液层下的幽门生物膜。总之，一种新的方法，含药物的LPNs，可以穿透粘液层，有效地消除H。pylori生物膜为治疗持续性H.幽门感染。
The resistance of Helicobacter pylori (H. pylori) to conventional antibiotic treatments becomes prevalent recently. The biofilm formation was found to be highly correlated with the antibiotic resistance of H. pylori in the last decades. Moreover, H. pylori colonizes on the digestive tract epithelium located under the mucus layers, which further reduces therapeutic efficacy as mucus layers trap and remove exogenous substances including drugs. Herein, we reported a novel lipid polymer nanoparticles (LPNs) to overcome both biofilm and mucus layers obstruction. LPNs employed chitosan nanoparticle (CS NPs) as the core, mixed lipid layer containing rhamnolipids (RHL) as the shell and the surface of LPNs was further modified with DSPE-PEG2000 to improve hydrophilicity. Clarithromycin (CLR), a first-line drug for H. pylori infection, was encapsulated in LPNs. LPNs, especially the formulation utilizing 100% of RHL as the lipid shell, exhibited excellent eradicating ability to H. pylori biofilm, which was mainly reflected in the significant reduction of biofilm biomass and viability, destruction of biofilm architecture and elimination of extracellular polymeric substances (EPS). The anti-biofilm activities of LPNs are related to: 1) the disrupting effect of RHL on biofilm matrix; 2) antibacterial effects of CLR and CS NPs on biofilm bacteria and 3) inhibitory effects of CS NPs and RHL on bacteria adhesion and biofilm formation. Furthermore, PEGylated LPNs could rapidly penetrate through mucus without interacting with mucins and effectively eradicate H. pylori biofilm under mucus layer. In conclusion, a novel approach of drug-containing LPNs that could penetrate through mucus layers and effectively eradicate H. pylori biofilm provides new ways to treat persistent H. pylori infections.