Are skin patches the future of mRNA vaccine technology?

Cold chain storage remains one of the most persistent barriers to mRNA vaccine access, adding cost and logistical complexity to distribution, particularly in lower-resource settings.

In ‘Exploring an Alternative to mRNA Vaccine Cold Chain Storage: MRNA-Lipid Nanoparticle Stability When Dried in a Polymer Matrix’ published recently in Advanced Functional Materials, researchers from the Royal Melbourne Institute of Technology, the Massachusetts Institute of Technology and Harvard Medical School explored ways to solve this problem.

Lipid nanoparticles (LNPs) are the delivery vehicles of the vaccine particles and are typically stored at temperatures between −90°C and −15°C in a water-based solution. These fragile particles are prone to collapse during processing, which may render them ineffective.

Microneedle patches, which deliver vaccines through hundreds of tiny polymer tips that dissolve in the skin, have been proposed as an alternative to injectable vaccines that require refrigeration. The patches also offer ease of application compared with traditional injections. Earlier MIT-led research demonstrated that such patches could be printed and stored at room temperature using a model mRNA system, theoretically improving vaccine access.

This latest study examines what happens to LNPs when they are dried into the polymer material used to make microneedle patches. Specifically, researchers looked to explain why certain dry patch formulations preserve particle function better than others.

The patch material is a blend of two polymers, PVP and PVA, combined in equal parts. Earlier lab work had identified this ration as a formulation that preserves the mRNA's ability to function while remaining structurally firm enough to hold a microneedle's shape.

Researchers used two specialized imaging techniques to observe the particles directly: cryogenic transmission electron microscopy, which involves freezing samples to preserve their structure at an extremely small scale for close inspection, and in situ small-angle x-ray scattering, which uses x-rays to track molecular rearrangement as it happens in real time. Together, these tools let the team follow the mRNA particles through each stage of the process, as they were mixed into the patch material, dried and then rehydrated.

The imaging showed that as the particles dried out, their internal structure shifted, and the lipid molecules rearranged into a partially different packing pattern. Importantly, this shift wasn't permanent. When there was enough polymer relative to mRNA, at least 320 parts polymer to 1 part mRNA, the particles were able to return to their original structure once rehydrated. Both how the nanoparticles were designed and how much polymer surrounded them affected how well they held up through the drying and rehydrating process.

The authors noted that further work is needed before the approach can move toward clinical use. They plan to further optimize nanoparticle and patch formulations, as well as evaluate how well the dried and rehydrated patches generate an immune response.

Vaccines prevent approximately 4 million deaths in children every year. Yet, 1 in 5 children worldwide do not have access to life-saving vaccines. In 2024, 14.3 million infants worldwide received no vaccines at all. In the United States alone, the cold chain packaging market size was valued at $2.22 billion in 2025 and is expected to rise to $5.45 billion by 2033.

“This research is helping build the foundation for microneedle patches that could make advanced vaccines and therapies simpler to use and easier to access,” lead researcher and RMIT Distinguished Professor Calum Drummond, AO, said in a news release. “The long-term goal is to support technologies that are not only effective but also practical for the places and communities that need them most.”