Lipid nanoparticles (LNPs) are cornerstone delivery vehicles for mRNA, shielding against RNases, promoting lysosomal escape via ionizable lipids’ pH-dependent charge (neutral at pH 7.4, cationic in endosomes), and enabling tissue-specific targeting. Composition: ionizable lipid (50%, e.g., ALC-0315), helper lipid (10%, DSPC), cholesterol (38.5%), PEG-lipid (1.5%) for stealth. Formulation via microfluidic mixing yields ~100 nm particles with >90% encapsulation.
Routes: IM for vaccines (BNT162b2, systemic immunity), IV for liver (NTLA-2001), intratumoral for cancer. Barriers overcome: serum stability, reticuloendothelial clearance via PEG, endosomal fusion. Biodegradable lipids reduce accumulation.
Clinical: >10 approvals, e.g., mRNA-1273. Prospects: targeted LNPs with GalNAc for extrahepatic delivery.
Credits: Nature Reviews Materials (2021), PMC (2023). Word count: 218.
Leave a Reply