Liposomal resiquimod for the treatment of Leishmania donovani infection.
Liposomal resiquimod for the treatment of Leishmania donovani infection.
复制标题
脂质体瑞西莫德用于治疗杜氏利什曼原虫感染。
DOI：
10.1093/jac/dkt320
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Bachelder,EricM
中科院分区：
文献类型：
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作者：
Peine,KevinJ;Gupta,Gaurav;Brackman,DeannaJ;Papenfuss,TraceyL;Ainslie,KristyM;Satoskar,AbhayR;Bachelder,EricM
目的咪唑喹啉家族药物是toll样受体7/8激动剂，以前曾用于治疗皮肤利什曼病。由于咪唑喹啉类药物的疏水性，传统上它们不被系统地用于治疗内脏利什曼病。我们配制了雷昔莫特脂质体，一种咪唑喹啉，用于内脏利什曼病的全身治疗。方法采用挤压脂膜水合法将雷喹莫特包封在脂质体中。然后静脉注射这些脂质体治疗感染多诺瓦利什曼原虫的BALB/c小鼠。结果雷昔莫特脂质体治疗可显著降低小鼠肝脏、脾脏和骨髓的寄生虫载量。此外，雷昔莫特治疗增加干扰素-γ和白细胞介素-10的产生在抗原回忆试验。雷昔魁莫特在组织学和体外培养实验中显示为无毒。结论fda批准的雷昔莫德脂质体制剂治疗内脏利什曼病有良好的效果。
ObjectivesThe 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.MethodsBy using lipid film hydration with extrusion, we encapsulated resiquimod in liposomes. These liposomes were then injected intravenously to treat BALB/c mice infected withLeishmania donovani.ResultsTreatment 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 andin vitroculture experiments.ConclusionsFDA-approved resiquimod, in a liposomal formulation, displays promising results in treating visceral leishmaniasis.