This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF:D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease.

中文翻译：

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新型Nrf2活化剂和气雾剂性能增强剂的微颗粒/纳米颗粒粉末，用于靶向肺Nrf2 / Keap-1途径的肺部递送。

这项系统，全面的研究首次报告了采用颗粒工程设计技术定向递送至肺部的先进可吸入治疗性干粉剂的成功合理设计，该干粉剂包含富马酸二甲酯（一种用于治疗肺部炎症的一流Nrf2活化剂）。作为高级喷雾干燥（SD）单组分DPI。此外，具有高载药量的两组分共喷雾干燥（co-SD）DMF：D-Man DPI已成功设计为靶向肺部输送，作为采用封闭模式有机溶液高级喷雾干燥的高级DPI。基于组成和喷雾干燥参数，使用基于空气动力学特性的体外预测性肺部建模，使用实验设计（DoE）进行区域目标沉积。这些发现表明，在喷雾干燥中使用D-Man可以显着改善熔点较低的小分子的颗粒形成和气溶胶性能。这些固态的可吸入微粒/纳米颗粒在FDA批准的人类DPI装置中显示出出色的气溶胶分散性能。使用体外预测性肺沉积模型，这些颗粒的气溶胶沉积模式显示出能够到达下呼吸道以治疗该区域的急性肺损伤（ALI），慢性阻塞性肺疾病（COPD），肺动脉高压等炎症的能力（PH）和肺血管内皮疾病。这些固态的可吸入微粒/纳米颗粒在FDA批准的人类DPI装置中显示出出色的气溶胶分散性能。使用体外预测性肺沉积模型，这些颗粒的气溶胶沉积模式显示出能够到达下呼吸道以治疗该区域的急性肺损伤（ALI），慢性阻塞性肺疾病（COPD），肺动脉高压等炎症的能力（PH）和肺血管内皮疾病。这些固态的可吸入微粒/纳米颗粒在FDA批准的人类DPI装置中显示出出色的气溶胶分散性能。使用体外预测性肺沉积模型，这些颗粒的气溶胶沉积模式显示出能够到达下呼吸道以治疗该区域的急性肺损伤（ALI），慢性阻塞性肺疾病（COPD），肺动脉高压等炎症的能力（PH）和肺血管内皮疾病。