Tuberculosis (TB) has gained attention over the past few decades by becoming one of the top ten leading causes of death worldwide. This infectious disease of the lungs is orally treated with a medicinal armamentarium. However, this route of administration passes through the body's first-pass metabolism which reduces the drugs' bioavailability and toxicates the liver and kidneys. Inhalation therapy represents an alternative to the oral route, but low deposition efficiencies of delivery devices such as nebulizers and dry powder inhalers render it challenging as a favorable therapy. It was hypothesized that by encapsulating two potent TB-agents, i.e. Q203 and bedaquiline, that inhibit the oxidative phosphorylation of the bacteria together with a magnetic targeting component, superparamagnetic iron oxides, into a poly (D, L-lactide-co-glycolide) (PDLG) carrier using a single emulsion technique, the treatment of TB can be a better therapeutic alternative. This simple fabrication method achieved a homogenous distribution of 500 nm particles with a magnetic saturation of 28 emu/g. Such particles were shown to be magnetically susceptible in an in-vitro assessment, viable against A549 epithelial cells, and were able to reduce two log bacteria counts of the Bacillus Calmette-Guerin (BCG) organism. Furthermore, through the use of an external magnet, our in-silico Computational Fluid Dynamics (CFD) simulations support the notion of yielding 100% deposition in the deep lungs. Our proposed inhalation therapy circumvents challenges related to oral and respiratory treatments and embodies a highly favorable new treatment regime.

中文翻译：

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通过Q203，苯达喹啉和超顺磁性氧化铁（SPIO）在纳米颗粒聚集体中的三层封装，对肺结核（TB）进行主动肺靶向治疗。

在过去的几十年中，结核病（TB）已成为全球十大主要死因之一，因此受到关注。肺部的这种传染性疾病可通过药用武器库口服治疗。但是，这种给药途径是通过人体的首过代谢，这会降低药物的生物利用度并毒害肝脏和肾脏。吸入疗法是口服途径的替代方法，但是输送装置（如雾化器和干粉吸入器）的低沉积效率使其成为一种有利的疗法。假设通过将两种抑制细菌氧化磷酸化的强效TB试剂Q203和苯达喹啉与磁性靶向组分超顺磁性氧化铁一起封装到聚（D，L-丙交酯-乙交酯（PDLG）载体采用单乳化技术，可以治疗结核病，是一种更好的治疗选择。这种简单的制造方法实现了500 nm颗粒的均匀分布，磁饱和度为28 emu / g。此类颗粒在体外评估中显示出对磁敏感，对A549上皮细胞有活力，并且能够减少卡介苗芽孢杆菌（BCG）生物的两个对数细菌计数。此外，通过使用外部磁体，我们的计算机内计算流体动力学（CFD）模拟支持在深肺中产生100％沉积的概念。我们提出的吸入疗法可克服与口服和呼吸疗法相关的挑战，并体现了高度有利的新疗法。