Imperial College London
Alternate

Prof Milo Shaffer

Faculty of Natural Sciences, Department of Chemistry

Professor of Materials Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5825m.shaffer Website

 
 
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Assistant

 

Mr John Murrell +44 (0)20 7594 2845

 
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Location

 

401BMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ellis:2018:10.1021/acsnano.7b08264,
author = {Ellis, T and Chiappi, M and García-Trenco, A and Al-Ejji, M and Sarkar, S and Georgiou, TK and Shaffer, MSP and Tetley, TD and Schwander, S and Ryan, MP and Porter, AE},
doi = {10.1021/acsnano.7b08264},
journal = {ACS Nano},
pages = {5228--5240},
title = {Multimetallic microparticles increase the potency of rifampicin against intracellular Mycobacterium tuberculosis},
url = {http://dx.doi.org/10.1021/acsnano.7b08264},
volume = {12},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 disorder of intracellular M.tb. MMPs were effective at independently driving membrane destruction of extracellular bacilli located at the exterior face of THP1 macrophages. This MMP system presents as an effective drug delivery vehicle that could be used for the transport of antituberculous drugs such as rifampicin to infected alveolar macrophages, while increasing drug potency. By increasing M.tb membrane permeability, such a system may prove effectual in improving treatment of drug-susceptible TB in addition to M.tb strains considered drug-resistant.
AU  - Ellis,T
AU  - Chiappi,M
AU  - García-Trenco,A
AU  - Al-Ejji,M
AU  - Sarkar,S
AU  - Georgiou,TK
AU  - Shaffer,MSP
AU  - Tetley,TD
AU  - Schwander,S
AU  - Ryan,MP
AU  - Porter,AE
DO  - 10.1021/acsnano.7b08264
EP  - 5240
PY  - 2018///
SN  - 1936-0851
SP  - 5228
TI  - Multimetallic microparticles increase the potency of rifampicin against intracellular Mycobacterium tuberculosis
T2  - ACS Nano
UR  - http://dx.doi.org/10.1021/acsnano.7b08264
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29767993
UR  - https://pubs.acs.org/doi/10.1021/acsnano.7b08264
UR  - http://hdl.handle.net/10044/1/60100
VL  - 12
ER  -
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