PEG lipids
PEG lipids are found in the exterior shell of the LNP and serve a couple of key functions including:1 providing steric hindrance to prevent aggregation and 2 promoting a small particle size. PEG-lipids are also used to prevent proteins from binding to LNPs and increase systemic circulation times and mediate indirect targeting capabilities of LNPs. The ability of LNPs formulated with PEG-lipids to bypass the reticulo-endothelial clearance system and stay in systemic circulation gives them their nickname - “stealth agents”.
Explore our cGMP PEG offering:
ALC-0159
ALC-0159 is a polyethylene glycol (PEG)-lipid conjugate also called a PEGylated lipid. ALC-0159 is a lipid excipient that can be used to form lipid nanoparticles (LNPs).
DMG-PEG 2000
DMG-PEG2000 is a synthetic PEGylated lipid containing myristoyl diglyceride. DMG-PEG2000 is frequently used in LNP formulations for mRNA vaccines and other nucleic acid delivery applications.
DSPE PEG2000
DSPE-PEG2000 is a synthetic PEGylated lipid derivative of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine. DSPE-PEG2000 has been found to display a better anchoring ability than short-chain PEG lipids in membranes and thereby increase LNP circulation time.
While PEG-lipids have long been the standard for LNP formulations, they also present a few challenges including:
- Steric hindrance of long PEG chains hinders the ability of a cell to uptake the therapeutic
- PEGylation also hinders endosomal escape of nanoparticles, leading to decreased activity of the delivery system
- Repeated administration of PEGylated systems can result in a phenomenon called accelerated blood clearance (ABC).
Other alternatives to PEG-lipids in LNPs are being explored, and recent work has identified polysarcosine (pSar)-lipids as a promising alternative. pSar-lipids, a polymer-lipid conjugate based on the amino acid sarcosine, have demonstrated similar stealth properties to PEG-lipids. Previous studies have also shown polysarcosine lipids to induce a lower immunogenic response than PEG-lipids when administered to rabbits, zebrafish embryos, and mice. And most recently, pSar-lipids were evaluated in mRNA-LNPs and displayed high RNA transfection ability and an improved safety profile. Avanti is now offering pSar-lipids with varying polymeric chain lengths and lipid chain lengths for your PEG-free mRNA delivery research! Discover polysarcosine lipids as an alternative to PEG-lipids today!
Explore other GMP lipids:
Why partner with us?
Support from concept to commercial
It starts with having the leading lipid technology experts in synthesis and formulation and approaching the discovery process in a collaborative nature, then having the expertise to transfer those learnings into a GMP manufacturing environment to support clinical development. And finally, having the commercial production capability to support launch and commercial supply.
Our full range of services include process chemistry, scale-up manufacturing, supply chain management with analytical and regulatory requirements. Our experienced staff of chemists and lipid analysts are ready to meet your development needs with pre-clinical through phase III and commercial launch, speak to one of our experts today!
Lipid supporting services
1. Hald Albertsen C, Kulkarni JA, Witzigmann D, Lind M, Petersson K, Simonsen JB. The role of lipid components in lipid nanoparticles for vaccines and gene therapy.
2. Adv Drug Deliv Rev. 2022 Sep;188:114416. doi: 10.1016/j.addr.2022.114416. Epub 2022 Jul 3.