Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying.
Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying.
复制标题
DOI：
10.3390/pharmaceutics7030233
复制
发表时间：
2015-08-26
期刊：
影响因子：
5.4
通讯作者：
Okamoto H
中科院分区：
文献类型：
--
作者：
Okuda T;Suzuki Y;Kobayashi Y;Ishii T;Uchida S;Itaka K;Kataoka K;Okamoto H
本研究以聚天冬氨酸（PAsp，DET）均聚物和聚乙二醇-聚天冬氨酸（PEG-PAsp，DET）共聚物两种生物可降解聚阳离子为载体，采用喷雾冷冻干燥法制备了可吸入干基因粉。所制备的基因干粉具有球形和多孔结构，直径为5~10 μm，且在制备过程中质粒DNA的完整性得以保持。此外，明确了基于PEG-PAsp（DET）的干基因粉末可以比基于PAsp（DET）的干基因粉末更充分地保持粉末生产后重构的聚合复合物的物理化学性质和体外基因转染效率。从使用Andersen级联撞击器的体外吸入研究中，证明了添加l-亮氨酸可以显著改善通过SFD制备的干粉的吸入性能。经肺给药后，与我们先前报道的基于壳聚糖的干基因粉末相比，基于PAsp（DET）和PEG-PAsp（DET）的干基因粉末在肺中可以实现更高的基因转染效率。
In this study, two types of biodegradable polycation (PAsp(DET) homopolymer and PEG-PAsp(DET) copolymer) were applied as vectors for inhalable dry gene powders prepared by spray freeze drying (SFD). The prepared dry gene powders had spherical and porous structures with a 5~10-μm diameter, and the integrity of plasmid DNA could be maintained during powder production. Furthermore, it was clarified that PEG-PAsp(DET)-based dry gene powder could more sufficiently maintain both the physicochemical properties and in vitro gene transfection efficiencies of polyplexes reconstituted after powder production than PAsp(DET)-based dry gene powder. From an in vitro inhalation study using an Andersen cascade impactor, it was demonstrated that the addition of l-leucine could markedly improve the inhalation performance of dry powders prepared by SFD. Following pulmonary delivery to mice, both PAsp(DET)- and PEG-PAsp(DET)-based dry gene powders could achieve higher gene transfection efficiencies in the lungs compared with a chitosan-based dry gene powder previously reported by us.