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通过反相蒸发法制备的脂质体:乙酰甲喹对伊氏锥虫的体外和体内疗效

Liposomes produced by reverse phase evaporation: in vitro and in vivo efficacy of diminazene aceturate against Trypanosoma evansi.

作者信息

Oliveira Camila Belmonte, Rigo Lucas Almeida, Rosa Luciana Dalla, Gressler Lucas Trevisan, Zimmermann Carine Eloise Prestes, Ourique Aline Ferreira, DA Silva Aleksandro Schafer, Miletti Luiz C, Beck Ruy Carlos Ruver, Monteiro Silvia Gonzalez

机构信息

Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Brazil.

Department of Production and Control of Medicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Brazil.

出版信息

Parasitology. 2014 May;141(6):761-9. doi: 10.1017/S0031182013002114. Epub 2014 Jan 28.

Abstract

This study aimed to develop and test the in vitro and in vivo effectiveness of diminazene aceturate encapsulated into liposomes (L-DMZ) on Trypanosoma evansi. To validate the in vitro tests with L-DMZ, the efficacy of a commercial formulation of diminazene aceturate (C-DMZ) was also assessed. The tests were carried out in culture medium for T. evansi, at concentrations of 0.25, 0.5, 1, 2 and 3 μg mL(-1) of L-DMZ and C-DMZ. A dose-dependent effect was observed for both formulations (L-DMZ and C-DMZ), with the highest dose-dependent mortality of trypomastigotes being observed at 1 and 3 h after the onset of tests with L-DMZ. The results of in vivo tests showed the same effects in the animals treated with L-DMZ and C-DMZ in single doses of 3.5 mg kg(-1) and for 5 consecutive days (3.5 mg kg(-1) day(-1)). It was possible to conclude that T. evansi showed greater in vitro susceptibility to L-DMZ when compared with C-DMZ. In vivo tests suggest that treatment with the L-DMZ and C-DMZ showed similar efficacy in vivo. The potential of the formulation developed in this study was clearly demonstrated, as it increased the efficacy of the treatment against trypanosomosis, but more studies are needed to increase the effectiveness in vivo.

摘要

本研究旨在开发并测试包裹于脂质体中的乙酰甲喹(L-DMZ)对伊氏锥虫的体外和体内有效性。为验证L-DMZ的体外测试结果,还评估了市售乙酰甲喹制剂(C-DMZ)的疗效。测试在伊氏锥虫培养基中进行,L-DMZ和C-DMZ的浓度分别为0.25、0.5、1、2和3 μg mL(-1)。两种制剂(L-DMZ和C-DMZ)均观察到剂量依赖性效应,在用L-DMZ进行测试开始后1小时和3小时观察到最高的剂量依赖性无鞭毛体死亡率。体内测试结果显示,以3.5 mg kg(-1)的单剂量连续5天(3.5 mg kg(-1) day(-1))用L-DMZ和C-DMZ治疗的动物中出现相同效果。可以得出结论,与C-DMZ相比,伊氏锥虫在体外对L-DMZ表现出更高的敏感性。体内测试表明,用L-DMZ和C-DMZ治疗在体内显示出相似的疗效。本研究中开发的制剂的潜力得到了明确证明,因为它提高了对锥虫病的治疗效果,但还需要更多研究来提高体内有效性。

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