Microfluidic Platform Enables Shearless Aerosolization of Lipid Nanoparticles for mRNA Inhalation

Area of Science:

• Biotechnology
• Gene Therapy
• Nanomedicine

Background:

• Pulmonary drug delivery offers advantages for gene therapy.
• Conventional vibrating mesh nebulizers damage nanoparticles during aerosolization, hindering mRNA delivery.
• Existing methods face challenges like particle aggregation and loss of mRNA encapsulation.

Purpose of the Study:

• To introduce a microfluidic aerosolization platform (MAP) for safe and efficient pulmonary mRNA delivery.
• To evaluate MAP's performance against vibrating mesh nebulizers.
• To assess the efficacy and safety of MAP-generated nanoparticles for lung-specific gene therapy.

Main Methods:

• Development of a microfluidic aerosolization platform (MAP).
• Comparison of MAP with vibrating mesh nebulizers for aerosolizing mRNA-loaded lipid nanoparticles.
• Assessment of nanoparticle integrity (morphology, aggregation, mRNA encapsulation).
• Evaluation of transfection efficiency in cell lines and *in vivo* lung-specific delivery in mice.

Main Results:

• MAP preserved the structural and physicochemical integrity of lipid nanoparticles.
• MAP avoided particle aggregation, mRNA loss, and nanoparticle deformation seen with vibrating mesh nebulizers.
• Aerosolized nanoparticles from MAP showed enhanced transfection efficiency.
• *In vivo* studies confirmed successful lung-specific mRNA transfection without toxicity.

Conclusions:

• The microfluidic aerosolization platform (MAP) is superior to vibrating mesh nebulizers for pulmonary mRNA delivery.
• MAP enables safe and efficient delivery of intact mRNA-loaded nanoparticles to the respiratory system.
• MAP represents a significant advancement for pulmonary gene therapy applications.