Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish

Biomacromolecules
Jiří TrousilMartin Hrubý

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 p...Continue Reading

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Citations

Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Arturo SánchezJahir Orozco
Apr 25, 2020·Frontiers in Chemistry·Małgorzata ŚwiętekDaniel Horák
Nov 30, 2021·Disease Models & Mechanisms·Nils-Jørgen Knudsen DalNoelia Alonso-Rodriguez

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