Targeted nasal delivery of LNP-mRNAs aerosolised by Rayleigh breakup technology.

Abstract

The nasal delivery of mRNA vaccines attracts great interests in both academia and industry. While the lipid nanoparticle (LNP)-mRNA complexes are vulnerable and need a subtle process for aerosolisation. In this study, a new nasal atomizer, based on the working rationale of Rayleigh breakup, was employed to aerosolise LNP-mRNAs. The data revealed no statistical differences in physiochemical properties before and after aerosolisation, strongly suggesting LNP-mRNAs be well preserved upon aerosolisation by Rayleigh breakup technology. Additionally, these Rayleigh breakup droplets showed a physical size of ∼25 µm in mean with a narrow size distribution (Span: 1.24) and demonstrated a large portion (70-80 % w/w) greater than 10 µm in aerodynamic diameter, strongly suggesting a predominate deposition in the upper airway and designating a great appropriateness for nasal drug delivery. Furthermore, the recently developed Alberta Idealized Nasal Inlet (AINI) was utilized to evaluate the regional nasal deposition of LNP-mRNA aerosols. It was demonstrated that, at the administration angle of 45°, the major deposition of mRNAs (>50 % w/w) was in the target region of turbinates. The inhalation airflow at 7.5 L/min can maximize the targeted delivery of mRNA (∼64 % w/w) and minimize the undesirable depositions in other segments. This study provides a new approach to aerosolise LNP-mRNAs with undisturbed stabilities for targeted nasal vaccine delivery.