pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with 'On' and 'Off'" pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.4. The QL-liposomes had a negative zeta potential at pH 7.4 that switched to a positive charge at acidic pH. VCM release from the liposome was quicker at pH 6 than pH 7.4. The OA-QL-liposome showed 4-fold lower MIC at pH 7.4 and 8- and 16-fold lower at pH 6.0 against both MSSA and MRSA compared to the bare drug. OA-QL liposome had a 1266.67- and 704.33-fold reduction in the intracellular infection for TPH-1 macrophage and HEK293 cells respectively. In vivo studies showed that the amount of MRSA recovered from mice treated with formulations was 189.67 and 6.33-fold lower than the untreated and bare VCM treated mice respectively. MD simulation of the QL lipid with the phosphatidylcholine membrane (POPC) showed spontaneous binding of the lipid to the bilayer membrane both electrostatic and Van der Waals interactions contributed to the binding. These studies demonstrated that the 'On' and 'Off' pH responsive liposomes enhanced the activity targeted and intracellular delivery VCM.

中文翻译：

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具有 pH 响应“开和关”开关的脂质体，用于靶向和细胞内输送抗生素

pH 响应给药系统是解决细菌对当前使用的抗生素耐药性扩散的新策略之一。本研究的目的是配制具有“开”和“关”pH 响应开关的脂质体，用于感染位点靶向。加载万古霉素 (VCM) 的脂质体的大小低于 100 nm，pH 为 7.4。QL 脂质体具有阴性pH 7.4 下的 zeta 电位在酸性 pH 下转为正电荷。VCM 在 pH 6 下从脂质体中释放比 pH 7.4 快。OA-QL-脂质体在 pH 7.4 和 8-和 16-下的 MIC 低 4 倍与裸药相比，在 pH 6.0 时对 MSSA 和 MRSA 的抑制作用降低了 1 倍。OA-QL 脂质体对 TPH-1 巨噬细胞和 HEK293 细胞的细胞内感染分别降低了 1266.67 和 704.33 倍。体内研究表明，从用制剂处理的小鼠中回收的 MRSA 量分别比未处理和裸 VCM 处理的小鼠低 189.67 和 6.33 倍。具有磷脂酰胆碱膜 (POPC) 的 QL 脂质的 MD 模拟表明，静电和范德华相互作用都有助于结合，脂质与双层膜的自发结合。这些研究表明，“开”和“关”pH 响应脂质体增强了靶向活性和细胞内递送 VCM。具有磷脂酰胆碱膜 (POPC) 的 QL 脂质的 MD 模拟表明，静电和范德华相互作用都有助于结合，脂质与双层膜的自发结合。这些研究表明，“开”和“关”pH 响应脂质体增强了靶向活性和细胞内递送 VCM。具有磷脂酰胆碱膜 (POPC) 的 QL 脂质的 MD 模拟表明，静电和范德华相互作用都有助于结合，脂质与双层膜的自发结合。这些研究表明，“开”和“关”pH 响应脂质体增强了靶向活性和细胞内递送 VCM。