Résumés disponibles (85) :

DA COSTA GOUVEIA Joana (UMR8204-U1019 éq. 07 - Priscille BRODIN)
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@mail :  joana.gouveia@ibl.cnrs.fr      tél. :  0320871166


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Titre de la communication :
Pulmonary co-administration of the synergic drugs Ethionamide and Booster using aerosolized nanoparticles: a promising strategy to treat tuberculosis
Auteurs (et leurs adresses) de la communication :
Joana Costa-Gouveia*, Priscille Brodin* *Université de Lille, CNRS UMR8204, Inserm U1019, CHU Lille, Institut Pasteur de Lille, Centre d\'Infection et d\'Immunité de Lille (CIIL), 59000 Lille, France
Résumé de la communication :
Tuberculosis (TB) is a leading cause of death worldwide. The use of ethionamide (ETH), an important second line anti-TB drug, is hampered by low oral bioavailability and the onset of severe side effects. Recently discovered “booster”, molecules strongly increasing the efficacy of ETH, could restore the use of this drug and thus improve the current clinical outcome of drug-resistant TB. To investigate the simultaneously delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated the synergic compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of the 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) NPs displayed the best physiochemical characteristics and were selected for in vivo studies. The NPs suspension, administered directly into mice lungs using a Microsprayer®, led to a significant decrease of the pulmonary bacterial load 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.

Acknowledgments: Financial support for this work was provided by the European Community (CycloN Hit Grant n° 608407), the Feder (12001407 (D-AL) Equipex Imaginex BioMed) and the Region Nord Pas de Calais (convention n° 12000080).

DA COSTA GOUVEIA Joana (UMR8204-U1019 éq. 07 - Priscille BRODIN)