Antisense oligonucleotides and their technical suitability to nebulization.
Int J Pharm
; 661: 124390, 2024 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-38936443
ABSTRACT
In vivo studies investigating the inhalative efficacy of biotherapeutics, such as nucleic acids, usually do not perform an aerosolization step, rather the solution is directly administered into the lungs e.g. intratracheally. In addition, there is currently very little information on the behavior of nucleic acid solutions when subjected to the physical stress of the nebulization process. In this study, the aim was to assess the technical suitability of Locked Nucleic Acids (LNAs), as a model antisense oligonucleotide, towards nebulization using two commercially available nebulizers. A jet nebulizer (Pari LC Plus) and a vibrating mesh nebulizer (Aerogen Solo) were employed and solutions of five different LNAs investigated in terms of their physical and chemical stability to nebulization and the quality of the generated aerosols. The aerosol properties of the Aerogen Solo were mainly influenced by the viscosity of the solutions with the output rate and the droplet size decreasing with increasing viscosity. The Pari LC Plus was less susceptible to viscosity and overall the droplet size was smaller. The LNAs tolerated both nebulization processes and the integrity of the molecules was shown. Chemical stability of the molecules from the Aerogen Solo was confirmed, whereas aerosol generation with the Pari LC Plus jet nebulizer led to a slight increase of phosphodiester groups in a fully phosphorothiolated backbone of the LNAs. Overall, it could be shown that nebulization of different LNAs is possible and inhalation can therefore be considered a potential route of administration.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nebulizadores e Vaporizadores
/
Oligonucleotídeos Antissenso
/
Aerossóis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article