Magallanes M, Dijkstra J, Fierer J
Department of Medicine and Pathology, University of California San Diego School of Medicine, La Jolla 92093.
Antimicrob Agents Chemother. 1993 Nov;37(11):2293-7. doi: 10.1128/AAC.37.11.2293.
We used a dehydration-rehydration procedure in order to efficiently incorporate ciprofloxacin into phospholipid vesicles (liposomes), which we then used to treat BALB/c mice that had been infected per os with Salmonella dublin. A single injection of liposome-incorporated ciprofloxacin (LIC) was 10 times more effective than a single injection of free drug at preventing mortality. When free ciprofloxacin was administered twice daily for 5 days, it was more effective than when it was administered as a single dose. Treatment with LIC produced dose-dependent decreases in bacterial counts in spleen, stool, and Peyer's patches, indicating that the drug had distributed to all areas of inflammation, not just to the major reticuloendothelial system organs. Although LIC was cleared rapidly from the blood, drug persisted in the liver and spleen for at least 48 h after administration of a dose of LIC. We attribute the enhanced activity of LIC to the concentration and persistence of active drug in the infected organs. Our results confirm the fact that ciprofloxacin is effective therapy for systemic salmonella infection and show that LIC is even more effective than aqueous ciprofloxacin in our model.
我们采用脱水-再水化程序，以便将环丙沙星有效地包入磷脂囊泡（脂质体）中，随后我们用其治疗经口感染都柏林沙门氏菌的BALB/c小鼠。在预防死亡率方面，单次注射包载环丙沙星的脂质体（LIC）比单次注射游离药物有效10倍。当游离环丙沙星每日给药两次，持续5天时，其效果比单次给药更好。LIC治疗使脾脏、粪便和派尔集合淋巴结中的细菌计数呈剂量依赖性下降，这表明药物分布到了所有炎症部位，而不仅仅是主要的网状内皮系统器官。尽管LIC从血液中迅速清除，但在给予一剂LIC后，药物在肝脏和脾脏中至少持续存在48小时。我们将LIC活性增强归因于活性药物在感染器官中的浓度和持久性。我们的结果证实了环丙沙星是治疗全身性沙门氏菌感染的有效疗法这一事实，并表明在我们的模型中，LIC比水性环丙沙星更有效。
