PEG-Lipid Nanoparticles in the Development of mRNA Vaccines

Automated Solutions and In-Situ PAT to Support LNP Formulation

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<center>Structure of a lipid nanoparticle (LNP) containing mRNA molecules for COVID-19 vaccine therapy</center>
Structure of a lipid nanoparticle (LNP) containing mRNA molecules for COVID-19 vaccine therapy

1. PEG Lipids
Higher stability and longer circulation


2. Helper Lipids
Structural support


3. mRNA
Coding spike protein fragments = API


4. Cholesterol
Structural support and rigidity


5. Cationic Lipids
Stabilization of mRNA

automated PAT for formulation of PEG-lipid nanoparticles LNP for mRNA production

Downstream Processing Techniques


Related Resources

Citations and References

  1. Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials, 6(12), 1078–1094.
  2. Santonocito, D., Sarpietro, M. G., Carbone, C., Panico, A., Campisi, A., Siciliano, E. A., Sposito, G., Castelli, F., & Puglia, C. (2020). Curcumin containing PEGylated solid lipid nanoparticles for systemic Administration: a preliminary study. Molecules, 25(13), 2991.
  3. Prabhu, S., Ortega, M. S., & Ma, C. (2005). Novel lipid-based formulations enhancing the in vitro dissolution and permeability characteristics of a poorly water-soluble model drug, piroxicam. International Journal of Pharmaceutics, 301(1–2), 209–216.


Více informací


What is PEG?

PEG (polyethylene glycol) is a synthetic polymer that is commonly used in various industries including pharmaceuticals, cosmetics, and food. PEG is a hydrophilic substance, meaning it is attracted to water and readily dissolves in it. In pharmaceuticals, PEG is often used as a solubilizing agent for poorly soluble drugs. It can also be used to modify the pharmacokinetic properties of drugs by increasing their half-life, reducing their clearance rate, and improving their bioavailability.

What is a PEG-lipid? What is a Pegylated lipid?

PEG-lipid, also called pegylated lipid, is a type of lipid that is modified with a polyethylene glycol (PEG) chain. This modification helps to improve the stability of the lipid nanoparticles, which are used to deliver mRNA vaccines into cells. The PEG-lipid acts as a shield, preventing the immune system from recognizing and attacking the nanoparticles before they can deliver their payload. "Payload" refers to the therapeutic or diagnostic substance carried by the nanoparticles. This is crucial for the effectiveness of mRNA vaccines, as it allows the vaccine to reach its target cells and initiate an immune response. Thus, developing PEG-lipid has been a crucial breakthrough in the fight against COVID-19.

Does lipid adhere or stick to PEG?

In general, lipids do not adhere or stick to PEG. However, the interaction between lipids and PEG can be influenced by a number of factors, such as the size and shape of the lipid molecule, the length and molecular weight of the PEG chain, and the concentration and temperature of the solution. In some cases, lipids may associate with PEG through hydrophobic interactions or van der Waals forces. However, these interactions are typically weak and reversible and do not result in a significant amount of adhesion or sticking between the two molecules.

Why use PEG lipids?

PEG lipids have various effects on the properties of lipid nanoparticles such as particle size and stability. PEG lipids can also be utilized to attach specific ligands to the particle for targeted delivery. By optimizing the proportions and properties of PEG lipids, chemists can potentially enhance the efficacy of drug delivery and overcome the limitations of poorly soluble drugs. Additionally, PEG lipids are often used as an excipient in pharmaceutical formulations, including vaccines, due to their biocompatibility and ability to improve drug solubility and stability. Both the Moderna and Pfizer-BioNTech COVID-19 vaccines use PEG-lipids as an excipient, which is a substance that is added to a vaccine formulation to improve its stability and effectiveness.

How does PEG increase circulation time?

PEG (polyethylene glycol) can increase the circulation time of drugs or drug carriers, such as lipid nanoparticles, by reducing their recognition and elimination by the immune system. Specifically, when PEG molecules are attached to the surface of the drug or drug carrier, they form a protective layer that shields it from detection by the body's immune cells. This is because PEG is a hydrophilic polymer that is not recognized as foreign by the immune system, and therefore it is not subject to the same clearance mechanisms that are responsible for eliminating foreign substances from the body. This protective effect is sometimes referred to as the "stealth effect" or "PEGylation", and it can significantly improve the pharmacokinetic properties of drugs or drug carriers, such as lipid nanoparticles, by increasing their circulation time in the bloodstream.