Muco-Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery.

ABSTRACT: Intranasal delivery of mRNA vaccines offers promising opportunities to combat airborne viruses like SARS-CoV-2 by provoking mucosal immunity, which not only defends against respiratory infection but also prevents contagious transmission. However, the development of nasal mRNA vaccines has been hampered by the lack of effective means to overcome the mucus barrier. Herein, ionizable lipid-incorporated liquid lipid nanoparticles (iLLNs) capable of delivering mRNA cargo across airway mucosa are designed. Adjusting the ratios of ionizable and cationic lipids allows fine-tuning of the pK_a of iLLNs to the range of nasal mucosal pH (5.5-6.5), thus facilitating mucus penetration via the formation of near-neutral, PEGylated muco-inert surfaces. When nasally administered to mice, the top c

SUBMITTER: Maniyamgama N 

PROVIDER: S-EPMC11923898 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature