Levy M Y, Polacheck I, Barenholz Y, Benita S
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
J Med Vet Mycol. 1993;31(3):207-18. doi: 10.1080/02681219380000261.
A submicron amphotericin B (AmB) sterile emulsion with a mean droplet size of approximately 100 nm was prepared. The emulsion was stable at 4 degrees C over a period of 4 months. The acute toxicity results showed that the maximum tolerated dose of the AmB emulsion was 2.0 mg kg-1 as compared to 0.5 mg kg-1 for a commercial deoxycholate suspension, Fungizone. Efficacy evaluations of submicron AmB emulsion compared to Fungizone were performed in a murine candidiasis model using either a single or a multiple daily dose administration of 0.4 mg kg-1. Survival (100%) was observed up to 15-18 days post-infection in mice treated with AmB emulsion or Fungizone, while all control non-treated animals had died after 9 days in both single and multi-treatment experiments. Survival (50%) was obtained after 35 days in the single treatment, and 40 days in the multi-treatment, experiment with AmB emulsion, while treatment with Fungizone gave 50% survival after 15 and 20 days, respectively. The overall results indicate that in murine candidiasis, treatment with AmB submicron emulsion was more effective than Fungizone, suggesting a potential therapeutic application.
制备了一种平均液滴尺寸约为100 nm的亚微米两性霉素B（AmB）无菌乳剂。该乳剂在4℃下4个月内保持稳定。急性毒性结果表明，AmB乳剂的最大耐受剂量为2.0 mg kg-1，而市售的去氧胆酸盐混悬液Fungizone的最大耐受剂量为0.5 mg kg-1。在小鼠念珠菌病模型中，使用0.4 mg kg-1的单次或每日多次剂量给药，对亚微米AmB乳剂与Fungizone进行疗效评估。在用AmB乳剂或Fungizone治疗的小鼠中，感染后15 - 18天观察到存活率为100%，而在单次和多次治疗实验中，所有未治疗的对照动物在9天后均死亡。在单次治疗实验中，使用AmB乳剂35天后存活率为50%，多次治疗实验中40天后存活率为50%，而使用Fungizone治疗分别在15天和20天后存活率为50%。总体结果表明，在小鼠念珠菌病中，用AmB亚微米乳剂治疗比Fungizone更有效，提示其具有潜在的治疗应用价值。
