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Published on: May 20, 2016
Intranasal Delivery of mRNA Polyplexes via Rayleigh Breakup Aerosols: An In Vitro Method for Nasal Deposition and
Mazen Kafienah1, Ziheng Zheng2, Hao-Ying Li3
1GKT School of Medical Education, Faculty of Life Sciences and Medicine, King's College London.
A novel Rayleigh breakup nasal atomizer gently aerosolizes messenger RNA (mRNA) vectors, preserving their integrity for effective intranasal delivery and gene expression in respiratory disease treatments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Respiratory Medicine
Background:
- Intranasal mRNA delivery offers direct immune activation for respiratory diseases.
- Conventional aerosolization damages non-viral mRNA vectors due to shear forces.
- Maintaining mRNA vector integrity is crucial for therapeutic efficacy.
Purpose of the Study:
- To develop a non-destructive method for aerosolizing mRNA therapeutics for intranasal delivery.
- To preserve the physicochemical properties and biological activity of polyethyleneimine (PEI)-mRNA vectors during aerosolization.
- To evaluate the nasal deposition and cellular delivery of aerosolized mRNA polyplexes.
Main Methods:
- Utilized a Rayleigh breakup nasal atomizer for gentle aerosolization of PEI-mRNA polyplexes.
- Characterized mRNA polyplexes (particle size, polydispersity index, zeta potential) pre- and post-aerosolization.
- Assessed aerosol deposition patterns using an Alberta Idealized Nasal Inlet (AINI) model.
- Evaluated cellular uptake and gene expression (GFP) in A549 lung epithelial cells.
Main Results:
- Rayleigh breakup aerosolization produced uniform droplets with minimal shear, preserving mRNA polyplex integrity.
- Physicochemical properties (particle size, PDI, zeta potential) remained stable post-aerosolization.
- Aerosolized mRNA predominantly deposited in the nasal turbinate regions.
- Delivered mRNA polyplexes successfully entered A549 cells, leading to detectable GFP expression.
Conclusions:
- Rayleigh breakup aerosolization is an effective, non-destructive method for intranasal mRNA delivery.
- This technique preserves mRNA vector integrity and biological function for targeted delivery.
- The study demonstrates a promising approach for developing intranasal mRNA-based therapeutics and vaccines.
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