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载吐酒石脂质体作为治疗利什曼病的新策略

Emetic Tartar-Loaded Liposomes as a New Strategy for Leishmaniasis Treatment.

作者信息

Coelho Larissa D, Souza Mirna M D, Cassali Geovanni D, Silva Raphaela A, Paiva Maria J N, Barros André L B, Teixeira Eliane M, Silveira Josianne N, Coelho Paulo M Z, Aguiar Marta M G, Oliveira Mônica C

机构信息

Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.

Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.

出版信息

Pharmaceutics. 2023 Mar 10;15(3):904. doi: 10.3390/pharmaceutics15030904.

Abstract

Emetic tartar (ET), was used in the treatment of leishmaniasis but its use was discontinued due to its low therapeutic index. Liposomes have been shown to be a promising strategy for delivery of bioactive substances in the region of interest, in order to reduce and/or eliminate undesirable effects. In the present study, liposomes containing ET were prepared and characterized to evaluate acute toxicity as well as their leishmanicidal action using BALB/c mice with an inoculum of () Liposomes were composed of egg phosphatidylcholine and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol, with an average diameter of 200 nm, zeta potential of +18 mV, and ET encapsulated into liposomes at a concentration near 2 g/L. Healthy mice were treated with ET or liposome containing ET (Lip-ET) in a single dose of 16 mg/kg of Sb intravenously and observed for 14 days. The death of two animals in the ET-treated group and no deaths in the Lip-ET-treated group was observed. Higher hepatic and cardiac toxicity were observed in animals treated with ET when compared to animals treated with Lip-ET, blank liposomes (Blank-Lip) and PBS. The study of antileishmanial efficacy was conducted by intraperitoneal administration of Lip-ET, for ten consecutive days. It was observed by limiting dilution that treatments with liposomal formulations containing ET, as well as Glucantime, led to a significant reduction in parasitic load in spleen and liver ( < 0.05) when compared to the untreated control group.

摘要

吐酒石(ET)曾用于治疗利什曼病,但由于其治疗指数低而停止使用。脂质体已被证明是在感兴趣区域递送生物活性物质的一种有前景的策略,以减少和/或消除不良影响。在本研究中,制备并表征了含有ET的脂质体,以评估其急性毒性以及对接种了()的BALB/c小鼠的杀利什曼原虫作用。脂质体由鸡蛋磷脂酰胆碱和3β-[N-(N',N'-二甲基氨基乙烷)-氨基甲酰基]胆固醇组成,平均直径为200nm,ζ电位为+18mV,ET以接近2g/L的浓度包封在脂质体中。健康小鼠以16mg/kg的Sb静脉内单剂量接受ET或含ET的脂质体(Lip-ET)治疗,并观察14天。观察到ET治疗组有两只动物死亡,而Lip-ET治疗组无死亡。与接受Lip-ET、空白脂质体(Blank-Lip)和PBS治疗的动物相比,接受ET治疗的动物观察到更高的肝脏和心脏毒性。通过连续十天腹腔注射Lip-ET进行抗利什曼原虫疗效研究。通过有限稀释观察到,与未治疗的对照组相比,用含ET的脂质体制剂以及葡糖胺治疗导致脾脏和肝脏中的寄生虫负荷显著降低(<0.05)。

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