Leveraging the extensive surface area of the lungs for
gene therapy,
inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through
inhalation, including severe damage to nanoparticles due to shearing forces. A microfluidic
aerosolization platform (MAP) can preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient mRNA delivery to the
respiratory system. Results demonstrated the superiority of the novel microfluidic aerosolizer over the conventional vibrating mesh
nebulizer, as it avoided problems such as
particle aggregation, loss of mRNA encapsulation, and deformation of
nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic
aerosolization platform led to enhanced
transfection efficiency across various
cell lines.
In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful,
lung-specific
mRNA transfection without
observable signs of
toxicity. This pioneering MAP represents a significant advancement for the pulmonary
gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.