Title:Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles
Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid,
or Ethambutol on Multidrug-Resistant Mycobacterium tuberculosis
Volume: 20
Issue: 3
Author(s): Huixian Jiang, Xiang Li, Zhenjian Xing, Qun Niu and Jiangping Xu*
Affiliation:
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
Keywords:
Multidrug-resistant Mycobacterium tuberculosis, poly (DL-lactide-co-glycolide), nanoparticle, anti-TB regimens, macrophage, bactericidal activity.
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.
