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Stability of Naked Nucleic Acids under Physical Treatment and Powder Formation: Suitability for Development as Dry
Tomoyuki Okuda1, Maki Okazaki1, Akihiko Hayano1
1Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Pharmaceutics
|December 23, 2023
Summary
Small interfering RNA (siRNA) is more stable than plasmid DNA (pDNA) for inhalation powders. siRNA maintains integrity through physical treatments and powder formation, unlike pDNA, making it ideal for respiratory drug delivery.
Area of Science:
- Biotechnology
- Pharmaceutics
- Molecular Biology
Background:
- Functional nucleic acids like plasmid DNA (pDNA) and small interfering RNA (siRNA) are emerging as therapeutic agents.
- Dry powder formulations for inhalation offer practical advantages for treating respiratory diseases.
Purpose of the Study:
- To compare the stability of naked pDNA and siRNA under various physical stresses and powder-forming processes.
- To evaluate the suitability of pDNA and siRNA for dry powder inhalation formulations.
Main Methods:
- Naked pDNA and siRNA were subjected to physical treatments including sonication, heating, and atomization.
- Two powder-forming processes, spray-drying and spray-freeze-drying, were employed.
- Structural and functional integrity of nucleic acids were assessed post-treatment and powder formation.
Main Results:
- pDNA's structural and functional integrity significantly decreased after physical treatments, while siRNA remained largely preserved.
- siRNA powders produced via spray-drying and spray-freeze-drying retained their integrity, unlike pDNA powders.
- A spray-freeze-dried siRNA powder (12% content) demonstrated excellent structural and functional integrity and high aerosol performance (40% fine particle fraction).
Conclusions:
- siRNA exhibits superior stability compared to pDNA in the naked state, making it more suitable for dry powder inhalation formulations.
- The findings support siRNA as a promising candidate for developing inhaled nucleic acid therapies for respiratory conditions.
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