TY - JOUR
T1 - Targeted nasal delivery of LNP-mRNAs aerosolised by Rayleigh breakup technology
AU - Li, Hao-Ying
AU - Paramanandana, Abhimata
AU - Kim, Sally Yunsun
AU - Granger, Luke
AU - Raimi-Abraham, Bahijja Tolulope
AU - Shattock, Robin
AU - Makatsoris, Charalampos
AU - Forbes, Ben
N1 - Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2025/3/15
Y1 - 2025/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85217934608&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2025.125335
DO - 10.1016/j.ijpharm.2025.125335
M3 - Article
C2 - 39933606
SN - 0378-5173
VL - 672
SP - 125335
JO - INTERNATIONAL JOURNAL OF PHARMACEUTICS
JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS
M1 - 125335
ER -