Thanks to microfluidic technology, different nano-delivery systems are becoming clinically viable. Using a novel and rapid microfluidic hydrodynamic focusing (MHF) method (lipids on chip) we developed self-adaptable liposomes (SLs) containing cefpodoxime proxetil (CP) for the treatment of skin infections caused by . SLs were optimized using different flow rate ratios in the MHF method and the final formulation CPT3 was found to be the best in terms of particle size (68.27 ± 01.15 nm), % entrapment efficiency (% EE: 82 ± 1.5), polydispersity (PDI: 0.2 ± 0.012), and degree of deformability (DOD: 4.7 ± 0.18 nm). Rats (Sprague Dawley) treated with a self-adaptable CPT3 liposomal formulation recuperate skin injury, exhibited reduced bacterial counts (<10 CFU/mL) in the wounded region, and completely restored (100 %) on day 21. Rat survival, dermal pharmacokinetics and relationship were also investigated. Rats treated with an even 10-fold higher dose (100 mg/kg/day) of CP using an equivalent CPT3 formulation did not show any symptoms of toxicity as revealed by hematological, biochemical, and internal organ assessment observations. Finally, the developed CPT3 formulation with special interest in patients with high-risk skin injuries not only delivered CP in a controlled manner but was also clinically effective and safe as it did not produce any serious adverse events even at 10× higher doses in the infected rats.

中文翻译：

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基于芯片实验室的自调节脂质体用于快速伤口愈合：深入的体外、体内和更高剂量毒性研究

得益于微流体技术，不同的纳米递送系统正在临床上变得可行。使用新型快速微流体流体动力聚焦（MHF）方法（芯片上的脂质），我们开发了含有头孢泊肟酯（CP）的自适应脂质体（SL），用于治疗由 . 在 MHF 方法中使用不同的流速比对 SL 进行了优化，发现最终配方 CPT3 在粒径 (68.27 ± 01.15 nm)、% 包封效率 (% EE: 82 ± 1.5)、多分散性 (PDI) 方面是最佳的: 0.2 ± 0.012) 和变形程度 (DOD: 4.7 ± 0.18 nm)。用自适应 CPT3 脂质体制剂治疗的大鼠 (Sprague Dawley) 可恢复皮肤损伤，受伤区域的细菌计数减少 (<10 CFU/mL)，并在第 21 天完全恢复 (100%)。 大鼠存活、皮肤药代动力学和关系也进行了调查。血液学、生化和内脏器官评估观察结果显示，使用等效 CPT3 制剂、甚至高 10 倍剂量（100 毫克/千克/天）的 CP 治疗的大鼠没有表现出任何毒性症状。最后，开发的 CPT3 制剂对高危皮肤损伤患者特别感兴趣，不仅以受控方式输送 CP，而且在临床上也有效且安全，因为即使在感染者中使用 10 倍高剂量，也不会产生任何严重的不良事件。老鼠。