2 research outputs found
Multimetallic Microparticles Increase the Potency of Rifampicin against Intracellular <i>Mycobacterium tuberculosis</i>
<i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) 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 <i>M.tb</i> 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 <i>M.tb</i>-infected macrophages.
Efficient uptake of MMPs by <i>M.tb</i>-infected THP1 cells
was demonstrated using an <i>in vitro</i> macrophage infection
model, with direct interaction between MMPs and <i>M.tb</i> 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 <i>M.tb.</i> 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 <i>M.tb</i> membrane permeability,
such a system may prove effectual in improving treatment of drug-susceptible
TB in addition to <i>M.tb</i> strains considered drug-resistant
Multimetallic Microparticles Increase the Potency of Rifampicin against Intracellular <i>Mycobacterium tuberculosis</i>
<i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) 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 <i>M.tb</i> 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 <i>M.tb</i>-infected macrophages.
Efficient uptake of MMPs by <i>M.tb</i>-infected THP1 cells
was demonstrated using an <i>in vitro</i> macrophage infection
model, with direct interaction between MMPs and <i>M.tb</i> 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 <i>M.tb.</i> 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 <i>M.tb</i> membrane permeability,
such a system may prove effectual in improving treatment of drug-susceptible
TB in addition to <i>M.tb</i> strains considered drug-resistant