Development and assessment of mucus penetrating lipoparticles for mRNA vaccine delivery

The success of mRNA vaccines against SARS-CoV-2 relies on LNP as delivery system and optimized mRNA sequences. However, their lipid-based soft nature implies that a nebulization/spray process could alter their composition and thus result in poor mRNA delivery to the lungs or nasal cavities due to mucus entrapment and lipid alterations [1,2]. To overcome this, we developed mucus-penetrating lipoparticles (mucLP) by adding a solid polylactic-acid core [3] and optimized lipid composition to improve mucus penetration and resistance to shear stress, ensuring more efficient respiratory mRNA delivery