Abstract
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.
Highlights
A key for successful gene therapy is whether or not therapeutic genes can be effectively delivered and internalized into targeted organs and cells
Morphological and size differences were not observed between dry powders of different compositions
These results indicate that the integrity of pDNA could be maintained during powder production by spray freeze drying (SFD)
Summary
A key for successful gene therapy is whether or not therapeutic genes can be effectively delivered and internalized into targeted organs and cells. The approach for gene therapy by systemic administration has some obstacles, including degradation by endonuclease in blood and non-targeted distribution, subsequently leading to poor therapeutic effects and adverse effects, such as the interferon response. The approach of local administration, which enables the direct delivery of therapeutic genes into target organs, has been examined [2]. Pulmonary administration is a powerful tool for achieving effective pulmonary gene therapy against several lung diseases, such as cystic fibrosis, α1-antitrypsin deficiency, and lung cancer, which are the target of our pulmonary gene delivery system, due to direct and noninvasive delivery into deep lung areas through the respiratory tract [3]. The development of inhalable aerosol systems for pulmonary gene delivery is critical for clinical use
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