基于巨噬细胞表型的结核分枝杆菌联合吸入性咪喹莫特-PLGA 纳米复合物粒子的小鼠模型。
A Mouse Model for Tuberculosis Combined With Inhalable Imiquimod-PLGA Nanocomposite Particles Based on Macrophage Phenotype.
机构信息
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan;
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.
出版信息
In Vivo. 2022 Sep-Oct;36(5):2166-2172. doi: 10.21873/invivo.12942.
BACKGROUND/AIM: In vivo models of tuberculosis are effective tools for developing new drugs. The objective of this study was to prepare in vivo models for tuberculosis by utilizing nanocomposite particles (NCPs) containing imiquimod-loaded poly(lactic-co-glycolic acid) nanoparticles.
MATERIALS AND METHODS
NCPs were prepared from dichloromethane with imiquimod and poly(lactic-co-glycolic acid) using a spray dryer. Mice were treated with NCPs in the lungs by inhalation, and then infection with Mycobacterium bovis bacille Calmette-Guerin was performed (treatment groups). The concentrations of the pro-inflammatory cytokines, tumor necrosis factor-α and interferon-γ were measured in bronchoalveolar lavage fluid using an enzyme-linked immunosorbent assay.
RESULTS
When animals were treated with NCPs, the concentrations of tumor necrosis factor-α and interferon-γ in bronchoalveolar lavage fluid were significantly higher than in animals not treated with NCPs. In addition, high bacterial counts and circular granuloma were observed.
CONCLUSION
NCPs prepared in this study enhanced the level of inflammation in the lungs and support the preparation of in vivo models of tuberculosis.
背景/目的：体内结核病模型是开发新药的有效工具。本研究的目的是利用负载咪喹莫特的聚（乳酸-共-乙醇酸）纳米粒制备体内结核病模型。
材料与方法
采用喷雾干燥法，用二氯甲烷制备负载咪喹莫特和聚（乳酸-共-乙醇酸）的纳米复合颗粒（NCPs）。通过吸入将 NCPs 递送至肺部，然后进行牛分枝杆菌卡介苗感染（治疗组）。采用酶联免疫吸附试验测量支气管肺泡灌洗液中促炎细胞因子肿瘤坏死因子-α和干扰素-γ的浓度。
结果
当用 NCPs 处理动物时，支气管肺泡灌洗液中肿瘤坏死因子-α和干扰素-γ的浓度明显高于未用 NCPs 处理的动物。此外，还观察到高细菌计数和环形肉芽肿。
结论
本研究制备的 NCPs 增强了肺部的炎症水平，支持了体内结核病模型的制备。
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