Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis
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DOI：
10.1016/j.ijantimicag.2007.08.008
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发表时间：
2008-01-01
影响因子：
10.8
通讯作者：
Pedrosa, J.
中科院分区：
文献类型：
--
作者：
Gaspar, M. M.;Cruz, A.;Pedrosa, J.
结核病 (TB) 是传染病中导致死亡的主要原因。抗分枝杆菌药物的渗透性低且难以进入受感染的巨噬细胞，因此需要长期使用高剂量的药物。脂质体优先积聚在巨噬细胞中，提高抗生素对抗细胞内寄生虫的功效。在目前的工作中，开发并表征了几种利福布丁（RFB）脂质体制剂，并将其体内特性与静脉内给药后的游离 RFB 进行了比较。通过测试 RFB 脂质体制剂，与游离 RFB 相比，给药后肝脏、脾脏和肺中的抗生素浓度更高 24 It。这些器官中 RFB 的浓度取决于脂质体脂质的刚性。用二棕榈酰磷脂酰胆碱:二棕榈酰磷脂酰甘油 (DPPC:DPPG) 制备的脂质体 RFB 制剂是最有效的，并被选择在播散性结核病小鼠模型中进行生物学评估。与用游离 RFB 治疗的小鼠相比，用 DPPC:DPPG RFB 制剂治疗的小鼠在脾脏（5.53 log(10) vs. 5.18 log(10)）和肝脏（5.79 log(10) vs. 5.41 log(10)）中表现出较低的细菌负荷。在肺部，接受封装 RFB 治疗的小鼠的病理水平较低。这些结果表明，脂质体 RFB 是治疗人类免疫缺陷病毒合并感染患者肺外结核的一种有前途的方法。 (C) 2007 Elsevier B.V. 和国际化疗协会。版权所有。
Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of anti mycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24 It post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidyl glycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients. (C) 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.