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Antisense oligonucleotides and their technical suitability to nebulization
Leonardo L Seidl1, Regina Moog2, Kirsten A Graeser2
1Roche Pharma Research and Early Development, Therapeutic Modalities, pCMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland; Technical University of Munich, TUM School of Natural Sciences, Boltzmannstr. 10, 85748 Garching, Germany.
Nebulization of Locked Nucleic Acids (LNAs) is feasible using jet and mesh nebulizers. This study confirms LNA stability, supporting inhalation as a potential delivery route for these biotherapeutics.
Area of Science:
- Pharmaceutical Sciences
- Biotechnology
Background:
- In vivo studies of inhaled biotherapeutics often bypass aerosolization.
- Limited data exists on nucleic acid behavior during nebulization.
Purpose of the Study:
- To evaluate the technical suitability of Locked Nucleic Acids (LNAs) for nebulization.
- To assess LNA physical and chemical stability and aerosol quality using two nebulizer types.
Main Methods:
- Tested five different LNA solutions with a jet nebulizer (Pari LC Plus) and a vibrating mesh nebulizer (Aerogen Solo).
- Analyzed LNA physical stability, chemical integrity, and aerosol characteristics (droplet size, output rate).
Main Results:
- Both nebulizers generated aerosols from LNA solutions, maintaining molecular integrity.
- Aerogen Solo's aerosol properties depended on solution viscosity.
- Pari LC Plus produced smaller droplets and showed minor chemical changes in phosphorothioated backbones.
Conclusions:
- Nebulization of LNAs is technically possible, indicating inhalation is a viable administration route.
- Nebulizer choice impacts aerosol properties and requires consideration of solution viscosity and LNA chemistry.
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