Carter K C, Baillie A J, Alexander J, Dolan T F
Pharmacy Department, Strathclyde University, Glasgow, UK.
J Pharm Pharmacol. 1988 May;40(5):370-3. doi: 10.1111/j.2042-7158.1988.tb05271.x.
A study of the antileishmanial efficacy of sodium stibogluconate was carried out in BALB/c mice. The drug was administered to Leishmania donovani-infected animals on days 7 and 8 post-infection in one of three forms; free (40-50 mg Sbv Kg-1), liposomal, or niosomal (6.4-8.0 mg Sbv Kg-1) drug. On day 14 post-infection counts of the number of parasites present in the liver, spleen and bone marrow of treated and control animals showed that although all three drug preparations significantly reduced parasite numbers in the liver (approximately equal to 99% suppression) they had little effect on those residing in the spleen or bone marrow. The carrier forms of the drug were therefore significantly more effective than free drug in reducing liver parasite burdens. Increasing the concentration and the number of doses of free drug (maximum of 500 mg Sbv Kg-1), and reducing the size of the vesicles used to deliver the drug had a minimal effect on parasite numbers in the spleen and bone marrow. It is proposed that because of the resistance of spleen and bone marrow parasites to drug therapy, the BALB/c mouse infected with L. donovani provides an excellent model system for the study of drug delivery to these deeper tissue sites.
在BALB/c小鼠身上开展了一项关于葡糖酸锑钠抗利什曼原虫疗效的研究。在感染后的第7天和第8天，以三种形式之一将该药物给予感染杜氏利什曼原虫的动物；游离药物（40 - 50 mg Sbv Kg-1）、脂质体药物或非离子表面活性剂泡囊药物（6.4 - 8.0 mg Sbv Kg-1）。在感染后第14天，对治疗组和对照组动物肝脏、脾脏和骨髓中存在的寄生虫数量进行计数，结果显示，尽管所有三种药物制剂均显著降低了肝脏中的寄生虫数量（抑制率约等于99%），但它们对脾脏或骨髓中的寄生虫影响很小。因此，在减轻肝脏寄生虫负荷方面，药物的载体形式比游离药物显著更有效。增加游离药物的浓度和剂量次数（最大为500 mg Sbv Kg-1），以及减小用于递送药物的囊泡大小，对脾脏和骨髓中的寄生虫数量影响极小。有人提出，由于脾脏和骨髓中的寄生虫对药物治疗具有抗性，感染杜氏利什曼原虫的BALB/c小鼠为研究药物向这些更深层组织部位的递送提供了一个极好的模型系统。
