Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Zebrafish MeSH
- Humans MeSH
- Macrophages * metabolism microbiology MeSH
- Disease Models, Animal MeSH
- Mycobacterium tuberculosis growth & development MeSH
- Mice MeSH
- Nanoparticles * chemistry therapeutic use MeSH
- Drug Carriers * chemistry pharmacokinetics pharmacology MeSH
- RAW 264.7 Cells MeSH
- Rifampin * chemistry pharmacokinetics pharmacology MeSH
- Tuberculosis drug therapy metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Drug Carriers * MeSH
- Rifampin * MeSH
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.
Department of Biosciences University of Oslo Blindernveien 31 0371 Oslo Norway
Institute of Experimental Physics Slovak Academy of Sciences Watsonova 47 040 01 Košice Slovakia
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