脂质体瑞喹莫德治疗感染杜氏利什曼原虫。
Liposomal resiquimod for the treatment of Leishmania donovani infection.
机构信息
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
出版信息
J Antimicrob Chemother. 2014 Jan;69(1):168-75. doi: 10.1093/jac/dkt320. Epub 2013 Aug 16.
OBJECTIVES
The imidazoquinoline family of drugs are Toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. Because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. We formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis.
METHODS
By using lipid film hydration with extrusion, we encapsulated resiquimod in liposomes. These liposomes were then injected intravenously to treat BALB/c mice infected with Leishmania donovani.
RESULTS
Treatment with liposomal resiquimod significantly decreased the parasite load in the liver, spleen and bone marrow. In addition, resiquimod treatment increased interferon-γ and interleukin-10 production in an antigen recall assay. Resiquimod was shown to be non-toxic in histology and in vitro culture experiments.
CONCLUSIONS
FDA-approved resiquimod, in a liposomal formulation, displays promising results in treating visceral leishmaniasis.
目的
咪唑并喹啉类药物是 Toll 样受体 7/8 激动剂，先前已被用于治疗皮肤利什曼病。由于咪唑并喹啉类药物的疏水性，它们传统上不被用于治疗内脏利什曼病的全身治疗。我们将脂溶性瑞喹莫德（一种咪唑并喹啉）制成脂质体，用于治疗内脏利什曼病的全身治疗。
方法
通过脂质体薄膜水化和挤压，我们将瑞喹莫德包封在脂质体中。然后将这些脂质体静脉注射到感染利什曼原虫的 BALB/c 小鼠体内进行治疗。
结果
用脂质体瑞喹莫德治疗可显著降低肝脏、脾脏和骨髓中的寄生虫负荷。此外，瑞喹莫德治疗可增加抗原再刺激试验中的干扰素-γ 和白细胞介素-10 产生。瑞喹莫德在组织学和体外培养实验中显示出无毒。
结论
在 FDA 批准的瑞喹莫德脂质体制剂中，显示出治疗内脏利什曼病的有前途的结果。
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