International journal of pharmaceutics: XOct 12, 2026

Distribution of mRNA-carrying lipid nanoparticles in the inner ear of newborn mice

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 13, 2026

Abstract

mRNA-loaded lipid nanoparticles produced widespread reporter expression in the cochlea following round window membrane delivery.

Lipid nanoparticles encapsulating mRNA were formulated using a systematic approach based on critical quality attributes.
In auditory cells, mRNA-loaded lipid nanoparticles resulted in a higher proportion of cells expressing the reporter gene compared to another delivery method, while overall protein levels remained similar.
Delivery via the round window membrane led to widespread expression across multiple cochlear regions, while scala media delivery showed limited expression confined to specific areas.
Hair cells did not exhibit detectable expression from either delivery method, indicating targeted distribution patterns.
The findings highlight the importance of administration routes in determining the distribution of mRNA delivery in the cochlea.

Simplified

Hearing loss affects millions worldwide, yet hearing aids and cochlear implants have major limitations. mRNA-based gene therapy could address the underlying molecular causes, but lipid nanoparticle (LNP) delivery in the inner ear remains underexplored and its biodistribution has not been systematically characterized. Here we establish and scale up an mRNA-encapsulated LNP formulation using a design-of-experiments (DoE) approach built on predefined critical quality attributes, and map the route-dependent distribution of reporter mRNA expression in the neonatal mouse cochlea. In HEI-OC1 auditory cells, mRNA-loaded LNPs produced a higher proportion of reporter-expressing cells and a more uniform distribution of expression than the cationic reagent Lipofectamine at a matched mRNA dose, while total reporter protein was comparable and metabolic viability was not reduced. We then compared cochlear distribution following round window membrane (RWM) delivery versus scala media administration. RWM delivery produced widespread reporter expression in perilymph-exposed compartments-the spiral ligament, the scala vestibuli and scala tympani regions, the stria vascularis and the spiral ganglion region-with no detectable expression in hair cells. Scala media injection produced a more restricted pattern, largely confined to the cuticular plate of inner and outer hair cells and part of the outer sulcus, with no expression in the spiral ganglion region or auditory nerve, indicating that this route does not distribute beyond the endolymphatic compartment. These results define the cochlear compartments accessible to LNP-mediated mRNA delivery and the dependence of that access on administration route, and provide the delivery map required for the design of LNP-based mRNA strategies in the inner ear.

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Distribution of mRNA-carrying lipid nanoparticles in the inner ear of newborn mice

Abstract

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