干粉吸入器
Zeta电位
粒径
吸入
材料科学
壳聚糖
喷雾干燥
吸入器
纳米技术
色谱法
化学工程
化学
生物医学工程
纳米颗粒
医学
有机化学
哮喘
工程类
内科学
解剖
作者
Hairui Zhang,Yajie Zhang,Robert O. Williams,Hugh D. C. Smyth
标识
DOI:10.1016/j.ijpharm.2021.120831
摘要
Gene therapy and more recently, gene editing is attractive via pulmonary delivery for enhanced regional targeting. However, processing of sensitive therapeutics into dry powders for inhalation can be problematic due to relatively stressful spraying or milling steps. Thin-film freeze-drying (TFFD) has attracted attention with its promising application in the production of DPI formulations possessing respirable particle size range (1–5 µm) particularly for thermally or shear sensitive therapeutics. In this study, gene editing dry powder formulations containing PEGylated chitosan/CRISPR-Cas9 nanocomplexes were prepared by TFFD. To evaluate stability during processing, nanocomplex size, zeta potential and transfection efficiency of reconstituted formulations were evaluated, and six potential DPI formulations were identified and characterized in terms of geometric particle size, powder surface morphology, and crystallinity. It was found that two formulations containing 3% mannitol with or without leucine were identified as suitable for inhalation with a desired aerodynamic performance. The flow rate dependency and inhaler dependency of these two formulations were also evaluated at different flow rates (60 L/min and 45 L/min) and different inhaler devices (RS01 DPI and HandiHaler) using NGI testing. This study demonstrated that TFFD processing of CRISPR-Cas9 polymer nanocomplexes resulted in a suitable dry powder for inhalation.
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