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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.

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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.

Keywords:
Antisense oligonucleotideInhalationLocked Nucleic AcidNebulizerStability

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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.