The acidic environment at bacterial infection sites is a potential external stimulus for targeted antibiotic delivery. This paper reports new biocompatible pH-sensitive lipids (PSLs) with three hydrocarbon tails, and a head group with a secondary amine and carboxylate function for site-specific nano delivery of vancomycin (VCM). PSLs formed stable liposomes with mean vesicle diameters and polydispersity indices between 99.38 ± 6.59 nm to 105.60 ± 5.38 nm and 0.161 ± 0.003 to 0.219 ± 0.05 respectively. The zeta potential values were negative at physiological pH (7.4) and shifted towards positivity with a decrease in pH. The encapsulation efficiency and loading capacity were in the range of 29–45% and 2.8–4.5% respectively. The VCM release increased and was more sustained at acidic pH than at the physiological pH. The molecular modeling studies revealed that structural changes in lipids at acidic pH could have caused the deformation of liposome structure and subsequent fast release. In vitro antibacterial activity revealed that the minimum inhibitory concentrations (MICs) of prepared liposomes at pH 6.5 were lower than the MICs at pH 7.4 against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) respectively. In addition, in vivo antibacterial activity study performed on two of the most active formulations showed that log₁₀ CFU/mL of MRSA recovered from TOAPA-VCM-Lipo and the TLAPA-VCM-Lipo treated mice were 1.5- and 1.8-fold lower than that found in bare VCM treated ones respectively.

细菌感染部位的酸性环境是靶向抗生素递送的潜在外部刺激。本文报道了新的具有3个碳氢化合物尾巴的生物相容性pH敏感脂质（PSL），以及具有仲胺和羧酸盐功能的头部基团，用于万古霉素（VCM）的位点特异性纳米递送。PSLs形成稳定的脂质体，其平均囊泡直径和多分散指数分别在99.38±6.59 nm至105.60±5.38 nm和0.161±0.003至0.219±0.05之间。在生理pH（7.4）时，ζ电位值为负，并随着pH的降低而向阳性转移。封装效率和负载能力分别在29–45％和2.8–4.5％的范围内。VCM的释放增加，在酸性pH值下比在生理pH值下更持久。体外抗菌活性表明，制备的脂质体在pH 6.5时的最低抑菌浓度（MIC）分别低于对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌（MRSA）的pH 7.4时的MIC 。此外，对两种活性最高的制剂进行的体内抗菌活性研究表明，从TOAPA-VCM-Lipo和TLAPA-VCM-Lipo处理的小鼠中回收的MRSA的log ₁₀ CFU / mL分别比其低1.5倍和1.8倍。分别在裸露的VCM处理过的中发现。