LNPs

Lipid nanoparticles (LNPs) are nanoscale particles composed of lipids that are used as delivery vehicles for therapeutic molecules, most notably nucleic acids such as messenger RNA (mRNA) and small interfering RNA (siRNA). LNPs protect payloads from degradation, improve cellular uptake, and facilitate release into the cytoplasm.

Typical LNP composition includes an ionizable or cationic lipid that carries a positive charge at acidic pH, helper lipids such as cholesterol and phospholipids (for example DSPC), and a polyethylene glycol (PEG)-lipid component that reduces nonspecific interactions and prolongs circulation. Some formulations incorporate targeting ligands to influence tissue distribution.

Delivery mechanism involves encapsulation of the nucleic acid within the lipid matrix. After administration, LNPs are taken up by cells via endocytosis. In the acidic endosome, ionizable lipids become protonated, promoting disruption of the endosomal membrane and release of the cargo into the cytoplasm.

Manufacturing often uses microfluidic mixing to achieve uniform particle sizes, typically in the 50–150 nanometer range. Critical quality attributes include particle size distribution, encapsulation efficiency, zeta potential, and stability under storage conditions. Cold-chain requirements are common for some incumbent formulations.

Applications include mRNA vaccines and therapeutics, such as vaccines against infectious diseases and treatments based on siRNA. LNPs have also been explored for delivering other nucleic acids, gene editing tools, and various drugs. First approved LNP-based siRNA drugs demonstrated clinical viability, and mRNA vaccines using LNPs have seen rapid deployment during the COVID-19 pandemic.

Safety considerations cover potential immunogenicity, infusion-related reactions, and PEG-related hypersensitivity in rare cases. Biodistribution after systemic administration often targets the liver and spleen, with ongoing work to achieve broader targeting and improved stability.