Garcia-Contreras Lucila, Sethuraman Vasu, Kazantseva Masha, Hickey Anthony
Division of Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Pharmaceutics. 2021 Aug 21;13(8):1309. doi: 10.3390/pharmaceutics13081309.
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.
脂质体作为单独的载体或与利福平（RIF）微粒（RMs）联合使用，被评估为增强RIF渗透到肉芽肿中的载体。RIF脂质体（RLs）通过0.1μm聚丙烯膜挤出。RMs采用溶剂蒸发法制备。感染四周后，将豚鼠（GPs）分为接受RM-RLs联合治疗或单独使用RLs治疗的组。RLs在挤出后进行雾化，而RMs悬浮在盐水中并在仅通过鼻腔吸入的舱室中对GPs进行雾化。治疗后进行尸检；切除肺和脾脏进行细菌学检查。RLs的平均直径为137.1±33.7nm，而RMs的投影面积直径为2.48μm。RMs的体积直径为64±1μm，表明RMs发生了聚集。与用空白脂质体治疗的豚鼠相比，用RLs治疗结核感染的豚鼠显著降低了其肺部细菌负荷和脾脏湿重。用RM-RLs治疗结核感染的动物也降低了其肺部细菌负荷和脾脏湿重，尽管这些降低在统计学上没有差异。基于这些结果，当RIF被包裹在通过肺部途径递送的脂质体中时其渗透到肉芽肿中的能力似乎增强了。
