Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model.

Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model.
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通过肺途径递送的组合利福平制剂治疗豚鼠模型中结核病的功效。

DOI:
10.3390/pharmaceutics13081309
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发表时间:
2021-08-21
期刊:
影响因子:
5.4
通讯作者:
Hickey A
Hickey A
中科院分区:
医学2区
文献类型:
--
作者:
Garcia-Contreras L;Sethuraman V;Kazantseva M;Hickey A

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脂质体作为单独的载体或与利福平 (RIF) 微粒 (RM) 组合,被评估为增强 RIF 渗透到肉芽肿中的载体。 RIF 脂质体 (RL) 通过 0.1 µm 聚丙烯膜挤出。 RMs是通过溶剂蒸发法制备的。感染后 4 周,豚鼠 (GP) 被分配到接受 RM-RL 组合治疗或单独 RL 治疗的组。 RL 在挤出后雾化,而 RM 悬浮在盐水中并在仅限鼻子的吸入室中雾化到 GP。治疗后进行尸检;切除肺和脾进行细菌学检查。 RL 的平均直径为 137.1 ± 33.7 nm,而 RM 的投影面积直径为 2.48 µm。 RM 的体积直径为 64 ± 1 µm,表明 RM 发生聚集。与空白脂质体治疗相比,用 RL 治疗感染结核病的 GP 显着降低了肺部细菌负荷和湿脾重量。用 RM-RL 治疗感染结核病的动物也减少了它们的肺部细菌负荷和湿脾重量,尽管这些减少没有统计学差异。基于这些结果,当将 RIF 封装到通过肺部途径递送的脂质体中时,RIF 向肉芽肿的渗透似乎得到增强。
Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment; the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.
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