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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid, or Ethambutol on Multidrug-Resistant Mycobacterium tuberculosis

Author(s): Huixian Jiang, Xiang Li, Zhenjian Xing, Qun Niu and Jiangping Xu*

Volume 20, Issue 3, 2023

Published on: 11 May, 2022

Page: [306 - 316] Pages: 11

DOI: 10.2174/1567201819666220511120215

Price: $65

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Multidrug-resistant Mycobacterium tuberculosis, poly (DL-lactide-co-glycolide), nanoparticle, anti-TB regimens, macrophage, bactericidal activity.

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