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Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis
[Image: see text] Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and bett...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718168/ https://www.ncbi.nlm.nih.gov/pubmed/30822386 http://dx.doi.org/10.1021/acsnano.8b07902 |
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author | Machelart, Arnaud Salzano, Giuseppina Li, Xue Demars, Aurore Debrie, Anne-Sophie Menendez-Miranda, Mario Pancani, Elisabetta Jouny, Samuel Hoffmann, Eik Deboosere, Nathalie Belhaouane, Imène Rouanet, Carine Simar, Sophie Talahari, Smaïl Giannini, Valerie Villemagne, Baptiste Flipo, Marion Brosch, Roland Nesslany, Fabrice Deprez, Benoit Muraille, Eric Locht, Camille Baulard, Alain R. Willand, Nicolas Majlessi, Laleh Gref, Ruxandra Brodin, Priscille |
author_facet | Machelart, Arnaud Salzano, Giuseppina Li, Xue Demars, Aurore Debrie, Anne-Sophie Menendez-Miranda, Mario Pancani, Elisabetta Jouny, Samuel Hoffmann, Eik Deboosere, Nathalie Belhaouane, Imène Rouanet, Carine Simar, Sophie Talahari, Smaïl Giannini, Valerie Villemagne, Baptiste Flipo, Marion Brosch, Roland Nesslany, Fabrice Deprez, Benoit Muraille, Eric Locht, Camille Baulard, Alain R. Willand, Nicolas Majlessi, Laleh Gref, Ruxandra Brodin, Priscille |
author_sort | Machelart, Arnaud |
collection | PubMed |
description | [Image: see text] Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB. |
format | Online Article Text |
id | pubmed-6718168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-67181682020-03-01 Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis Machelart, Arnaud Salzano, Giuseppina Li, Xue Demars, Aurore Debrie, Anne-Sophie Menendez-Miranda, Mario Pancani, Elisabetta Jouny, Samuel Hoffmann, Eik Deboosere, Nathalie Belhaouane, Imène Rouanet, Carine Simar, Sophie Talahari, Smaïl Giannini, Valerie Villemagne, Baptiste Flipo, Marion Brosch, Roland Nesslany, Fabrice Deprez, Benoit Muraille, Eric Locht, Camille Baulard, Alain R. Willand, Nicolas Majlessi, Laleh Gref, Ruxandra Brodin, Priscille ACS Nano [Image: see text] Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB. American Chemical Society 2019-03-01 2019-04-23 /pmc/articles/PMC6718168/ /pubmed/30822386 http://dx.doi.org/10.1021/acsnano.8b07902 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Machelart, Arnaud Salzano, Giuseppina Li, Xue Demars, Aurore Debrie, Anne-Sophie Menendez-Miranda, Mario Pancani, Elisabetta Jouny, Samuel Hoffmann, Eik Deboosere, Nathalie Belhaouane, Imène Rouanet, Carine Simar, Sophie Talahari, Smaïl Giannini, Valerie Villemagne, Baptiste Flipo, Marion Brosch, Roland Nesslany, Fabrice Deprez, Benoit Muraille, Eric Locht, Camille Baulard, Alain R. Willand, Nicolas Majlessi, Laleh Gref, Ruxandra Brodin, Priscille Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis |
title | Intrinsic
Antibacterial Activity of Nanoparticles
Made of β-Cyclodextrins Potentiates Their Effect as Drug
Nanocarriers against Tuberculosis |
title_full | Intrinsic
Antibacterial Activity of Nanoparticles
Made of β-Cyclodextrins Potentiates Their Effect as Drug
Nanocarriers against Tuberculosis |
title_fullStr | Intrinsic
Antibacterial Activity of Nanoparticles
Made of β-Cyclodextrins Potentiates Their Effect as Drug
Nanocarriers against Tuberculosis |
title_full_unstemmed | Intrinsic
Antibacterial Activity of Nanoparticles
Made of β-Cyclodextrins Potentiates Their Effect as Drug
Nanocarriers against Tuberculosis |
title_short | Intrinsic
Antibacterial Activity of Nanoparticles
Made of β-Cyclodextrins Potentiates Their Effect as Drug
Nanocarriers against Tuberculosis |
title_sort | intrinsic
antibacterial activity of nanoparticles
made of β-cyclodextrins potentiates their effect as drug
nanocarriers against tuberculosis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718168/ https://www.ncbi.nlm.nih.gov/pubmed/30822386 http://dx.doi.org/10.1021/acsnano.8b07902 |
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