Liposomes, a nanoscale drug delivery system, are well known for their ability to improve pharmacokinetics and reduce drug toxicity. In this work, maltoheptaose (G7)-presenting glycoliposomes were synthesized and evaluated in the delivery of the antibiotic rifampicin. Two types of liposomes were prepared: nonfluid liposomes from l-α-phosphatidylcholine (PC) and cholesterol, and fluid liposomes from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol). G7-derivatized glycolipid, G7-DPPE (DPPE: 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine), was incorporated into the liposomes at 21 and 14 μmol/mg to form nanoparticles of 75 ± 12 and 146 ± 14 nm for the nonfluid and fluid G7-glycoliposomes, respectively. The multivalent G7-glycoliposomes were characterized by lectin binding with concanavalin A (Con A). The dissociation constant K_d between Con A and the nonfluid or fluid G7-glycoliposomes was 0.93 or 0.51 μM, which represented ∼900- or 1600-fold stronger affinity than the binding between Con A and G7. The G7-glycoliposomes were loaded with rifampicin at 6.6 and 16 wt % encapsulation for the nonfluid and fluid G7-glycoliposomes, respectively. Introducing a carbohydrate in the liposomes slowed down the release of rifampicin, with the G7-glycoliposomes having the slowest release rate and the lowest permeability coefficient among the liposome formulations. The fluid G7-glycoliposomes lowered the minimal inhibitory concentration (MIC) of rifampicin against E. coli ORN208 by about 3 times, whereas liposomes without G7 or Man (d-mannose)-glycoliposomes showed no improvement in MIC. The rifampicin-loaded fluid G7-glycoliposomes demonstrated the best sustained antibacterial activity against E. coli, with up to 2 log reduction in the colony forming units at 4 × MIC after 24 h. Fluorescence resonance energy transfer and confocal fluorescence microscopy revealed stronger interactions of the bacterium with the fluid G7-glycoliposomes than other liposome formulations.

中文翻译：

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用于将利福平递送至大肠杆菌的麦芽七糖纳米级糖脂质体

脂质体是一种纳米级药物递送系统，以其改善药代动力学和降低药物毒性的能力而闻名。在这项工作中，合成了呈递麦芽七糖 (G7) 的糖脂质体，并在抗生素利福平的递送中进行了评估。制备了两种类型的脂质体：来自l -α-磷脂酰胆碱 (PC) 和胆固醇的非流体脂质体，以及来自 1,2-dipalmitoyl- sn -glycero-3-phosphocholine 和 1,2-dimyristoyl- sn -glycero - 3 的流体脂质体-磷酸-(1'-rac-甘油)。G7-衍生糖脂，G7-DPPE (DPPE: 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine) 以 21 和 14 μmol/mg 的浓度掺入脂质体中，分别形成非流体和流体 G7-糖脂质体的 75 ± 12 和 146 ± 14 nm 的纳米颗粒。多价 G7-糖脂质体的特征在于凝集素与伴刀豆球蛋白 A (Con A) 结合。解离常数K _dCon A 与非流体或流体 G7-糖脂质体之间的亲和力为 0.93 或 0.51 μM，其亲和力比 Con A 和 G7 之间的结合强 900 倍或 1600 倍。对于非流体和流体 G7-糖脂质体，G7-糖脂质体分别以 6.6 和 16 wt% 的利福平装载。在脂质体中引入碳水化合物减缓了利福平的释放，在脂质体制剂中，G7-糖脂质体具有最慢的释放速率和最低的渗透系数。流体 G7-糖脂质体将利福平对大肠杆菌ORN208的最小抑制浓度 (MIC) 降低了约 3 倍，而不含 G7 或 Man ( d-甘露糖)-糖脂质体的MIC没有改善。载有利福平的流体 G7-糖脂质体表现出对大肠杆菌的最佳持续抗菌活性，24 小时后 4 倍 MIC 时菌落形成单位减少高达 2 log。荧光共振能量转移和共聚焦荧光显微镜显示，与其他脂质体制剂相比，细菌与流体 G7-糖脂质体的相互作用更强。