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

被引：67

作者：

Costa-Gouveia, Joana ^{[1
]}

Pancani, Elisabetta ^{[2
]}

Jouny, Samuel ^{[1
]}

Machelart, Arnaud ^{[1
]}

Delorme, Vincent ^{[1
]}

Salzano, Giuseppina ^{[2
]}

Iantomasi, Raffaella ^{[1
]}

Piveteau, Catherine ^{[3
]}

Queval, Christophe J. ^{[1
]}

Song, Ok-Ryul ^{[1
]}

Flipo, Marion ^{[3
]}

Deprez, Benoit ^{[3
]}

Saint-Andre, Jean-Paul ^{[4
]}

Hureaux, Jose ^{[4
]}

Majlessi, Laleh ^{[5
]}

Willand, Nicolas ^{[3
]}

Baulard, Alain ^{[1
]}

Brodin, Priscille ^{[1
]}

Gref, Ruxandra ^{[2
]}

机构：

[1] Univ Lille, CNRS, INSERM, Inst Pasteur Lille,CHU Lille,U1019,UMR 8204,CIIL, F-59000 Lille, France

[2] Univ Paris Sud, Univ Paris Saclay, CNRS, Inst Mol Sci Orsay ISMO,UMR 8214, F-91405 Orsay, France

[3] Univ Lille, INSERM, Inst Pasteur Lille, Drugs & Mol Living Syst,U1177, F-59000 Lille, France

[4] Univ Hosp Ctr Angers, F-49000 Angers, France

[5] Inst Pasteur, Dept Genomes & Genet, Pathogenom Mycobacterienne Integree, Paris, France

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

PLGA NANOPARTICLES; AEROSOL DELIVERY; DRUG ETHIONAMIDE; CYCLODEXTRIN; SYSTEMS; MODEL; TOLERABILITY; MACROPHAGES; AGENT; MICE;

D O I：

10.1038/s41598-017-05453-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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" beta-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 (R), 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.

引用

页数：14

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