Optimization of a Dissolvable Lipid Nanoparticle Microneedle Formulation for mRNA Delivery Using Design of...

Area of Science:

• Biotechnology
• Materials Science
• Nanotechnology

Background:

• Microneedles (MNs) offer a minimally invasive method for transdermal delivery of lipid nanoparticles (LNPs).
• Optimizing LNP physicochemical properties and MN fabrication is crucial for effective delivery.
• Current optimization relies on trial-and-error, introducing researcher bias.

Purpose of the Study:

• To implement Design of Experiments (DoE) for unbiased optimization of LNP-MN fabrication parameters.
• To develop and validate an LNP-MN system for mRNA delivery.
• To assess the efficiency, homogeneity, and stability of mRNA delivery via LNP-MNs.

Main Methods:

• Utilized Design of Experiments (DoE) to systematically optimize LNP-MN fabrication.
• Developed LNP-MNs for delivering mRNA encoding green fluorescent protein (GFP).
• Evaluated transfection efficiency in mesenchymal stem cells and in vivo using luciferase mRNA in mice.

Main Results:

• Achieved 43.3% transfection efficiency in mesenchymal stem cells, significantly higher than the lipofectamine control (8.51%).
• Demonstrated homogeneous transfection (99.4% GFP positive cells) compared to the control (31.0%).
• Maintained 22.7% transfection efficiency after 42 days of room temperature storage and successfully transfected mice.

Conclusions:

• DoE provides a robust, unbiased method for optimizing LNP-MN fabrication.
• The developed mRNA-LNP-MN system shows high efficiency, homogeneity, and stability for transdermal delivery.
• This approach holds significant potential for advancing mRNA-based therapeutics and vaccines.