Patrick He1, Haiqiao Wang1, Yuan Zhang3, Ye Zhang1, Anthony Kelleher3, Chantelle Ahlenstiel3, Julie Suman4, Hui Xin Ong1,2, Daniela Traini1,2
1 Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2113, Australia
2 Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia
3 Kirby Institute, UNSW, Sydney, NSW 2052, Australia
4 Next Breath, an Aptar Pharma Company, Baltimore, MD 21227, USA
Summary
This study evaluates the physicochemical stability, aerosol characteristics, and nasal deposition of three lipid nanoparticle (LNP)-siRNA formulations (Moderna-like, Pfizer-like, and Alnylam-like) following aerosolisation using the LuerVax (Aptar Pharma) nasal spray device. Dynamic light scattering (DLS) showed that all formulations maintained monodisperse particle size distributions at around 100 nm post aerosolisation. The Moderna-like and Alnylam-like formulations showed slight increases in particle size and polydispersity index (PDI), while the Pfizer-like formulation remained unchanged. Zeta potential was preserved across all formulations.
Laser diffraction analysis showed consistent droplet size distributions across all formulations, with Dv(50) values around 380 µm and no droplets smaller than 10 µm, ideal for nasal deposition.
Encapsulation efficiency remained high (>90%) post-aerosolisation, though a decrease in encapsulated siRNA concentration suggested partial LNP disruption.
Deposition studies using the Alberta Idealized Nasal Inlet (AINI) model showed that over 80% of aerosolised siRNA deposited in the turbinate and around 10% in the vestibule, with minimal deposition in the olfactory region, nasopharynx, or lung regions. These results demonstrate the suitability of the LuerVax device for targeted intranasal delivery of LNP-siRNA therapeutics