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Pharmaceutics 2015, 7(3), 233-254; doi:10.3390/pharmaceutics7030233

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
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)
View Full-Text   |   Download PDF [3354 KB, uploaded 28 August 2015]   |  

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. 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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