Multimetallic Microparticles Increase the Potency of Rifampicin against Intracellular Mycobacterium tuberculosis

ACS Nano
Timothy EllisAlexandra E Porter

Abstract

Mycobacterium tuberculosis ( M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug-tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics. In this work, biodegradable multimetallic microparticles (MMPs), containing Ag NPs and ZnO NPs, were developed for use in pulmonary delivery of antituberculous drugs to the endosomal system of M.tb-infected macrophages. Efficient uptake of MMPs by M.tb-infected THP1 cells was demonstrated using an in vitro macrophage infection model, with direct interaction between MMPs and M.tb visualized with the use of electron FIB-SEM tomography. The release of Ag NPs and ZnO NPs within the macrophage endosomal system increased the potency of the model antibiotic rifampicin by as much as 76%, realized through an increase in membrane dis...Continue Reading

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Jun 21, 2019·Current Pharmaceutical Design·Prasad MinakshiGaya Prasad
Apr 14, 2020·International Journal of Nanomedicine·Alexandru-Flaviu TăbăranLucian Mocan
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Jan 3, 2019·Trends in Microbiology·Allon Weiner, Jost Enninga

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