Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying.
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.
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. tokuda@meijo-u.ac.jp.
Tomoyuki
T
Okuda
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. 124331505@ccalumni.meijo-u.ac.jp.
Yumiko
Y
Suzuki
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. g0673221@ccalumni.meijo-u.ac.jp.
Yuko
Y
Kobayashi
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656, Japan. tishii@bmw.t.u-tokyo.ac.jp.
Takehiko
T
Ishii
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. suchida@bmw.t.u-tokyo.ac.jp.
Satoshi
S
Uchida
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. itaka-ort@umin.net.
Keiji
K
Itaka
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656, Japan. kataoka@bmw.t.u-tokyo.ac.jo.|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. kataoka@bmw.t.u-tokyo.ac.jo.
Kazunori
K
Kataoka
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. okamotoh@meijo-u.ac.jp.
Hirokazu
H
Okamoto
biodegradable polycations; dry powder inhalers (DPIs); porous particles; pulmonary gene transfection; spray freeze drying (SFD)