Abdallah Ladaycia1, Ismael Hennia1, Dylan Antoniak2, Pauline Percier1, Philippe Rogueda2 & Remi Rosiere1
1InhaTarget Therapeutics, Rue Antoine de Saint Exupéry 2, 6041 Gosselies, Belgium
2Merxin Ltd., 1 Peterborough Road, Kings Lynn, PE30 5FQ, United Kingdom
Summary
Lipid nanoparticles (LNPs) represent a promising platform for delivering sensitive therapeutics, including nucleic acids, to the lungs. However, nebulization imposes challenges, as LNPs must resist shear forces, remain stable, and retain appropriate aerodynamic properties for deep lung deposition. This study evaluates the performance of the MRX004 soft-mist inhaler (SMI) in delivering LNPs containing nucleic acids. Three LNP formulations were tested: empty LNPs, LNPs entrapping oligonucleotides (LNP-ON), and LNPs entrapping mRNA (LNP-mRNA), all prepared with identical lipid compositions. The LNPs were characterized before and after aerosolization from the MRX004 device for particle size, zeta potential, entrapment efficiency (EE%), and aerodynamic properties. Results demonstrated that the MRX004 device successfully aerosolized all formulations with consistent shot weights and appropriate aerodynamic profiles for lung deposition. No significant changes were observed in particle size distribution or zeta potential after aerosolization, and the LNP tracer recovery was near 100%. LNP-ON showed a minor decrease in EE% (~7%) post-aerosolization, while LNP-mRNA remained stable. Aerodynamic particle size distribution metrics indicated that all formulations achieved mass median aerodynamic diameters between 4–5 µm, fine particle fractions around 40–46%, and deposition patterns consistent with deep lung delivery. The MRX004’s fine mist delivery preserved LNP integrity and ensured effective lung targeting. This study demonstrates that the MRX004 device effectively delivers nucleic acid-loaded LNPs while maintaining their physical properties, offering a promising strategy for lung-targeted therapies and vaccines.