Jiang Huixian, Li Xiang, Xing Zhenjian, Niu Qun, Xu Jiangping
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Department of Pharmacy, Guangzhou Chest Hospital, Guangzhou, China.
Curr Drug Deliv. 2023;20(3):306-316. doi: 10.2174/1567201819666220511120215.
Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear.
The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages.
Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds.
All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally.
The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.
耐多药结核分枝杆菌（MDR-TB）是结核病患者死亡的主要原因。纳米医学避免了传统药物治疗的一些局限性，并提高了抗细菌感染的治疗效果。然而，抗结核药物纳米颗粒（NP）化合物在抗MDR-TB治疗方案中的作用仍不明确。
本文旨在制备包裹左氧氟沙星、利奈唑胺、乙胺丁醇、丙硫异烟胺和吡嗪酰胺的纳米颗粒，并评估其在巨噬细胞中对MDR-TB的治疗效果。
采用复乳法制备载药聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒。在培养的巨噬细胞上研究这些纳米颗粒的共定位、细胞内释放和抗结核活性。在用纳米颗粒或游离药物化合物处理后，评估巨噬细胞的免疫表型，包括其线粒体膜电位、活性氧（ROS）和一氧化氮（NO）的产生。
所有载药PLGA纳米颗粒均呈球形，大小为150至210nm，包封率为14.22%至43.51%，并具有长效释放特性。载药PLGA纳米颗粒主要分布在巨噬细胞的细胞质中，具有较高的细胞相容性，并至少维持其浓度13天。与游离药物化合物相比，暴露于PLGA纳米颗粒化合物后的菌落数量明显减少。纳米颗粒化合物增强的抗菌活性可能是由于ROS和NO水平的提高，以及结核分枝杆菌感染的巨噬细胞内早期凋亡应激的增加。
PLGA纳米颗粒化合物的应用不仅提高了药物疗效，还诱导了巨噬细胞中的固有杀菌作用，证实这是一种有前途的MDR-TB治疗方法。
