PUBLICATION
Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish
- Authors
- Trousil, J., Syrová, Z., Dal, N.K., Rak, D., Konefal, R., Pavlova, E., Matějková, J., Cmarko, D., Kubíčková, P., Pavliš, O., Urbánek, T., Sedlak, M., Fenaroli, F., Raška, I., Stepanek, P., Hruby, M.
- ID
- ZDB-PUB-190221-8
- Date
- 2019
- Source
- Biomacromolecules 20(4): 1798-1815 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Drug Carriers*/chemistry
- Drug Carriers*/pharmacokinetics
- Drug Carriers*/pharmacology
- Humans
- Macrophages*/metabolism
- Macrophages*/microbiology
- Mice
- Mycobacterium tuberculosis/growth & development*
- Nanoparticles*/chemistry
- Nanoparticles*/therapeutic use
- RAW 264.7 Cells
- Rifampin*/chemistry
- Rifampin*/pharmacokinetics
- Rifampin*/pharmacology
- Tuberculosis/drug therapy*
- Tuberculosis/metabolism
- Tuberculosis/pathology
- Zebrafish
- PubMed
- 30785284 Full text @ Biomacromolecules
Citation
Trousil, J., Syrová, Z., Dal, N.K., Rak, D., Konefal, R., Pavlova, E., Matějková, J., Cmarko, D., Kubíčková, P., Pavliš, O., Urbánek, T., Sedlak, M., Fenaroli, F., Raška, I., Stepanek, P., Hruby, M. (2019) Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish. Biomacromolecules. 20(4):1798-1815.
Abstract
Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of alveolar macrophages. These cells avidly take up nanoparticles, even without the use of specific targeting ligands, making the use of nanotherapeutics ideal for the treatment of such infections. Methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) nanoparticles of several different polymer blocks' molecular weights and sizes (20-110 nm) were developed and critically compared as carriers for rifampicin, a cornerstone in tuberculosis therapy. The polymeric nanoparticles' uptake, consequent organelle targeting and intracellular degradation were shown to be highly dependent on the nanoparticles' physicochemical properties (the cell uptake half-lives 2.4-21 min, the degradation half-lives 51.6 min-ca 20 h after the internalization). We show that the nanoparticles are efficiently taken up by macrophages and are able to effectively neutralize the persisting bacilli. Finally, we demonstrate, using a zebrafish model of tuberculosis, that the nanoparticles are well tolerated, have a curative effect, and are significantly more efficient compared to a free form of rifampicin. Hence, these findings demonstrate that this system shows great promise, both in vitro and in vivo, for the treatment of tuberculosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping