Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid, or Ethambutol on Multidrug-Resistant
Humans
Mycobacterium tuberculosis
Pyrazinamide
/ pharmacology
Prothionamide
/ pharmacology
Ethambutol
/ pharmacology
Levofloxacin
/ pharmacology
Linezolid
/ pharmacology
Reactive Oxygen Species
Tuberculosis
Anti-Bacterial Agents
/ pharmacology
Polylactic Acid-Polyglycolic Acid Copolymer
/ therapeutic use
Tuberculosis, Multidrug-Resistant
/ drug therapy
Nanoparticles
Antitubercular Agents
Multidrug-resistant Mycobacterium tuberculosis
anti-TB regimens
bactericidal activity
macrophage
nanoparticle
poly (DL-lactide-co-glycolide)
Journal
Current drug delivery
ISSN: 1875-5704
Titre abrégé: Curr Drug Deliv
Pays: United Arab Emirates
ID NLM: 101208455
Informations de publication
Date de publication:
2023
2023
Historique:
received:
17
01
2022
revised:
27
03
2022
accepted:
30
03
2022
pubmed:
14
5
2022
medline:
9
2
2023
entrez:
13
5
2022
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 35546770
pii: CDD-EPUB-123363
doi: 10.2174/1567201819666220511120215
doi:
Substances chimiques
Pyrazinamide
2KNI5N06TI
Prothionamide
76YOO33643
Ethambutol
8G167061QZ
Levofloxacin
6GNT3Y5LMF
Linezolid
ISQ9I6J12J
dilactide
95-96-5
Reactive Oxygen Species
0
Anti-Bacterial Agents
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
Antitubercular Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
306-316Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.