Etanidazole in pH-sensitive liposomes:: Design, characterization and in vitro/in vivo anti-Trypanosoma cruzi activity
Etanidazole in pH-sensitive liposomes:: Design, characterization and in vitro/in vivo anti-Trypanosoma cruzi activity
复制标题
DOI：
10.1016/j.jconrel.2004.12.012
复制
发表时间：
2005-04-18
影响因子：
10.8
通讯作者：
Romero, EL
中科院分区：
文献类型：
--
作者：
Morilla, MJ;Montanari, J;Romero, EL
在这项工作中，将亲水性，低分子量和锥虫药物依他赛（ETZ）加载在pH敏感的脂质体（L-ETZ）中。脂质体由二烯酰基磷脂酰乙醇胺制成：胆固醇半核酸（涂料：Chems，6：4，Mol：Mol），为380 nm，在14％ETZ/总脂质（w/w）的比例为380 nm。为了通过荧光显微镜跟踪其摄取和细胞内命运，将pH敏感的脂质体加载到荧光团/淬灭剂对HPTS/DPX中。观察到脂质体水含量的快速递送到鼠J774巨噬细胞的细胞质中。 l-etz囊泡被未感染的克氏菌和锥虫感染的巨噬细胞吞噬。在经过L-ETZ处理的J774细胞上证明了72％的抗膨胀活性（AA），而相同剂量的自由ETZ呈现为0％AA。在14 mu g/鼠标剂量下，在14 mu g/house剂量下进行L-ETZ施用，引起了寄生虫感染的小鼠的寄生虫水平的显着降低。相反，接种180倍高剂量的游离ETZ在减少血液锥虫的数量时失败。因此，这些结果是开发系统的，例如L-ETZ，设计用于选择性递送到吞噬细胞的细胞质，从而增强了被认为是活性不佳的分子的功效。 （c）2004年由Elsevier B.V.出版
In this work, the hydrophilic, low molecular weight and trypanocidal drug etanidazole (ETZ) was loaded in pH-sensitive liposomes (L-ETZ). Liposomes were made of dioleoyl-phosphatidylethanolamine: cholesteryl hemisuccinate (DOPE:CHEMS, 6:4, mol:mol), of 380 nm size at 14% ETZ/total lipid (w/w) ratio. To follow their uptake and intracellular fate by fluorescence microscopy, pH-sensitive liposomes were loaded with the fluorophore/quencher pair HPTS/DPX. A fast and massive delivery of the liposomal aqueous content into the cytosol of murine J774 macrophages was observed. L-ETZ vesicles were phagocytosed by both uninfected and Trypanosoma cruzi-infected macrophages. A 72% of anti-amastigote activity (AA) was demonstrated on L-ETZ-treated J774 cells, whereas the same dose of free ETZ rendered 0% AA. Endovenous administration of L-ETZ at 14 mu g/mouse dose provoked significant decrease in parasitemia levels of T. cruzi-infected mice. Conversely, inoculation of a 180-fold higher dose of free ETZ failed in reducing the number of bloodstream trypomastigotes. Hence, these results point to develop systems, such as L-ETZ, designed for selective delivery of drugs to the cytoplasm of phagocytic cells, thus enhancing the efficacy of molecules considered poorly active. (c) 2004 Published by Elsevier B.V.