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Open AccessArticle

Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying

1
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
2
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656, Japan
3
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Niek Sanders
Pharmaceutics 2015, 7(3), 233-254; https://doi.org/10.3390/pharmaceutics7030233
Received: 29 May 2015 / Revised: 18 August 2015 / Accepted: 19 August 2015 / Published: 26 August 2015
(This article belongs to the Special Issue New Paradigm of Gene Therapy)
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. View Full-Text
Keywords: dry powder inhalers (DPIs); pulmonary gene transfection; biodegradable polycations; spray freeze drying (SFD); porous particles dry powder inhalers (DPIs); pulmonary gene transfection; biodegradable polycations; spray freeze drying (SFD); porous particles
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Okuda, T.; Suzuki, Y.; Kobayashi, Y.; Ishii, T.; Uchida, S.; Itaka, K.; Kataoka, K.; Okamoto, H. Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying. Pharmaceutics 2015, 7, 233-254.

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