Helper Lipids are a class of lipid molecules that increase particle stability and fluidity of lipid nanoparticles (LNP). Several classes of molecules were used as helper lipids such as phospholipids as exemplified by DSPC (Figure 1), cholesterol, PEGylated lipid.
The main benefits using Helper lipids in Lipid nanoparticles (LNPs) delivery vehicles is to improve the properties of the nanoparticle, such as particle stability, delivery efficacy, tolerability and biodistribution.
For example, cholesterol can enhance particle stability by modulating membrane integrity and rigidity. The molecular geometry of cholesterol derivatives can further affect delivery efficacy and biodistribution of lipid nanoparticles. cholesterol analogues with C-24 alkyl phytosterols increases the in vivo delivery efficacy of lipid nanoparticle-mRNA formulations.
Helper lipids with a cone-shape geometry favoring the formation hexagonal II phase, such as dioleoyl phosphatidylethanolamine (DOPE), can promote endosomal release of ONs.
Cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs.
PEGylated lipids (PEG lipids) can enhance LNP colloidal stability and circulation time in vivo, but it might reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation.
As a leading biochemical supplier worldwide, BroadPharm offer a wide array of Lipid molecules, such as Ionizable lipids, cationic lipids, helper lipids, PEG lipids to our clients worldwide. BroadPharm also provides fast speed custom synthesis of novel lipid molecules to empower your advanced research.
1. X Cheng, R. Lee, The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery, Adv Drug Deliv Rev, PMID: 26900977
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