Mechanistic and Strategic Insights into How Lipid Nanoparticles Interact with Membrane-Based Biological Barriers - PubMed
a day ago
- #lipid nanoparticles
- #drug delivery
- #biological barriers
- Lipid nanoparticles (LNPs) are a leading platform for nucleic acid delivery, with performance influenced by membrane-based biological barriers.
- Biological barriers exist at multiple levels, including extracellular matrices, mucosal layers, endothelial interfaces, plasma membranes, and intracellular organelles.
- LNP-membrane interactions are shaped by membrane biophysics, lipid chemistry, interfacial forces, and protein corona.
- Different administration routes (intramuscular, intravenous, intraperitoneal, inhaled, oral, intratumoral) affect biodistribution and targeting due to local architecture, fluid composition, and protein corona.
- Cellular membrane properties (surface chemistry, receptor expression, endocytic pathways) determine LNP binding and internalization in parenchymal, stromal, and immune cells.
- Intracellular trafficking and mRNA release involve endosomal maturation, acid-triggered lipid protonation, fusion-driven membrane remodeling, and nonbilayer phase transitions.
- LNP transcytosis occurs across restrictive barriers like the blood-brain barrier, tumor vasculature, pulmonary epithelium, and intestinal mucosa.
- Exocytosis and extracellular vesicles contribute to secondary mRNA delivery.
- Emerging experimental and computational tools are advancing the study of LNP-membrane interactions.
- Integration of molecular design with membrane biophysics and nanobio interface chemistry can guide next-generation LNP development.