Evaluation of rayleigh jet atomizer for intranasal delivery of lipid nanoparticle-siRNA formulations: stability, deposition, and device performance

Aug 17, 2025International journal of pharmaceutics

Testing a spray device for delivering lipid nanoparticle siRNA through the nose: stability, placement, and performance

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Abstract

The Rayleigh Jet Nasal Atomizer effectively delivers three lipid nanoparticle-based siRNA formulations to the nasal cavity.

Intranasal delivery targets the nasopharynx while reducing deposition in the lower respiratory tract.
Key nanoparticle characteristics were analyzed, including particle size distribution and encapsulation efficiency.
Although the structural integrity of LNPs was maintained, there was a reduction in encapsulated siRNA concentration, indicating potential disruption during aerosolisation.
The device's performance supports the feasibility of using LNP-siRNA formulations for non-invasive RNA-based therapeutics.

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The COVID-19 pandemic has emphasised the need for innovative and efficient drug delivery systems, particularly for nucleic acid-based therapeutics. Lipid nanoparticle (LNP)-based small interfering RNA (siRNA) technology provides a promising strategy for gene therapy, immune modulation, and targeted molecular medicine. Intranasal delivery of LNP-siRNA formulations offers advantages such as efficient gene silencing and non-invasive administration. However, the nasal spray device plays a crucial role in determining the deposition patterns within the nasal cavity and can impact the physicochemical stability of LNP formulations during aerosolisation. In this study, the Rayleigh Jet Nasal Atomizer was evaluated for its performance in delivering three LNP-siRNA formulations designed based on the LNP structures of Moderna, Pfizer, and Alnylam (Onpattro) marketed formulations, respectively. Key nanoparticle characteristics, including particle size distribution, polydispersity index (PDI), zeta potential, and encapsulation efficiency, as well as aerosol properties such as droplet size, were analyzed before and after aerosolisation. Deposition patterns were assessed using the Alberta Idealized Nasal Inlet (AINI) model to determine the distribution of aerosolized LNPs. The results demonstrate that the Rayleigh Jet Nasal Atomizer efficiently delivers all the three formulations to the nasal cavity, primarily targeting the nasopharynx, while minimizing deposition in the lower respiratory tract. Additionally, the device maintained LNPs structural integrity, although a reduction in encapsulated siRNA concentration suggests partial LNP disruption during aerosolisation. These findings indicate that the Rayleigh Jet Nasal Atomizer is a suitable device for intranasal delivery of LNP-based siRNA therapeutics, offering a promising approach for nasal administration of RNA-based drug delivery.

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Evaluation of rayleigh jet atomizer for intranasal delivery of lipid nanoparticle-siRNA formulations: stability, deposition, and device performance

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