Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles

Abstract Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered “booster” molecules strongly increase the ETH efficacy, opening new perspectives to improve the curr...

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Autores principales:	Joana Costa-Gouveia, Elisabetta Pancani, Samuel Jouny, Arnaud Machelart, Vincent Delorme, Giuseppina Salzano, Raffaella Iantomasi, Catherine Piveteau, Christophe J. Queval, Ok-Ryul Song, Marion Flipo, Benoit Deprez, Jean-Paul Saint-André, José Hureaux, Laleh Majlessi, Nicolas Willand, Alain Baulard, Priscille Brodin, Ruxandra Gref
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b72ffe20c51947b68f1019be57e2cb02
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spelling	oai:doaj.org-article:b72ffe20c51947b68f1019be57e2cb022021-12-02T11:52:59ZCombination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles10.1038/s41598-017-05453-32045-2322https://doaj.org/article/b72ffe20c51947b68f1019be57e2cb022017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05453-3https://doaj.org/toc/2045-2322Abstract Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered “booster” molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster. The efficacy of the designed formulations was evaluated in TB infected macrophages using an automated confocal high-content screening platform, showing that the drugs maintained their activity after incorporation in NPs. Among tested formulations, “green” β-cyclodextrin (pCD) based NPs displayed the best physico-chemical characteristics and were selected for in vivo studies. The NPs suspension, administered directly into mouse lungs using a Microsprayer®, was proved to be well-tolerated and led to a 3-log decrease of the pulmonary mycobacterial load after 6 administrations as compared to untreated mice. This study paves the way for a future use of pCD NPs for the pulmonary delivery of the [ETH:Booster] pair in TB chemotherapy.Joana Costa-GouveiaElisabetta PancaniSamuel JounyArnaud MachelartVincent DelormeGiuseppina SalzanoRaffaella IantomasiCatherine PiveteauChristophe J. QuevalOk-Ryul SongMarion FlipoBenoit DeprezJean-Paul Saint-AndréJosé HureauxLaleh MajlessiNicolas WillandAlain BaulardPriscille BrodinRuxandra GrefNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joana Costa-Gouveia Elisabetta Pancani Samuel Jouny Arnaud Machelart Vincent Delorme Giuseppina Salzano Raffaella Iantomasi Catherine Piveteau Christophe J. Queval Ok-Ryul Song Marion Flipo Benoit Deprez Jean-Paul Saint-André José Hureaux Laleh Majlessi Nicolas Willand Alain Baulard Priscille Brodin Ruxandra Gref Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
description	Abstract Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered “booster” molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster. The efficacy of the designed formulations was evaluated in TB infected macrophages using an automated confocal high-content screening platform, showing that the drugs maintained their activity after incorporation in NPs. Among tested formulations, “green” β-cyclodextrin (pCD) based NPs displayed the best physico-chemical characteristics and were selected for in vivo studies. The NPs suspension, administered directly into mouse lungs using a Microsprayer®, was proved to be well-tolerated and led to a 3-log decrease of the pulmonary mycobacterial load after 6 administrations as compared to untreated mice. This study paves the way for a future use of pCD NPs for the pulmonary delivery of the [ETH:Booster] pair in TB chemotherapy.
format	article
author	Joana Costa-Gouveia Elisabetta Pancani Samuel Jouny Arnaud Machelart Vincent Delorme Giuseppina Salzano Raffaella Iantomasi Catherine Piveteau Christophe J. Queval Ok-Ryul Song Marion Flipo Benoit Deprez Jean-Paul Saint-André José Hureaux Laleh Majlessi Nicolas Willand Alain Baulard Priscille Brodin Ruxandra Gref
author_facet	Joana Costa-Gouveia Elisabetta Pancani Samuel Jouny Arnaud Machelart Vincent Delorme Giuseppina Salzano Raffaella Iantomasi Catherine Piveteau Christophe J. Queval Ok-Ryul Song Marion Flipo Benoit Deprez Jean-Paul Saint-André José Hureaux Laleh Majlessi Nicolas Willand Alain Baulard Priscille Brodin Ruxandra Gref
author_sort	Joana Costa-Gouveia
title	Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
title_short	Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
title_full	Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
title_fullStr	Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
title_full_unstemmed	Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
title_sort	combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b72ffe20c51947b68f1019be57e2cb02
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Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles

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