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
The COVID-19 pandemic brought the importance of scientific research into sharp focus as scientists worked (and still work) tirelessly to develop effective vaccines and treatments to combat the virus and protect lives. A promising breakthrough in this pursuit has been the development and scale-up of lipid nanoparticles to deliver mRNA vaccines into cells. The success of this approach hinges on the stability of the lipid nanoparticles, emphasizing the importance of how the PEG-lipids are developed.
PEG (polyethylene glycol) is a hydrophilic synthetic polymer that is often used to aid the solubility and circulating half-life of therapeutics or vaccines by conjugating or modifying the surface of poorly soluble motifs or carrier transport molecules such as lipid nanoparticles. Prior to COVID-19, most pegylation methods were performed at small scale without sufficient characterization or control of process parameters that would enable rapid process scale-up.
AutoChem Solutions Enable Development from Prototype to Large-Scale Production
As the COVID-19 pandemic progressed, pharmaceutical companies, CDMOs, and CROs relied on METTLER TOLEDO solutions to speed up the development of PEG-lipids. Our products provided high-quality data the chemists needed to better understand their process, allowing them to complete investigations more quickly. Bioprocess reactors and integrated process analytical technology (PAT) helped scientists and engineers scale up from research and clinical-scale to large-scale production, which was essential during the urgent development of mRNA vaccines.
EasyMax™ synthesis workstations aided in obtaining valuable data on chemical reactions, optimizing processes, and reducing development times. The use of ReactIR™ in-situ FTIR provided real-time analysis of batch and flow reactions, while EasySampler™ enabled automated and robust inline methods for taking representative samples from reactions during overnight experimentation. ParticleTrack™ with FBRM® technology and EasyViewer™ inline microscopy were used to obtain insight into particle size, shape, and count. In addition to these solutions, METTLER TOLEDO iC Data Center was implemented by many to further streamline the research process through improved data capture, management, and analysis.
EasyViewer with iC Vision
Particle Size Analyzers
View and measure particles in situ and in real time. Read more
ParticleTrack with FBRM
Particle Size Analyzers
Understand, optimize, and control particles and droplets in real time. Read more
EasySampler
Automated Sampling System
Take samples inline, quench in situ, and dilute for reproducible analytical samples. Read more
The success of the PEG-lipid project has been a critical breakthrough in the fight against COVID-19, and the deployment of cutting-edge equipment and digitalization solutions at R&D sites has set the stage for further collaboration. This partnership between industry and technology providers highlights the crucial role that innovation can play in advancing scientific research. As the broader healthcare field addresses new and ongoing challenges, investments in similar technologies will be vital to overcoming them. METTLER TOLEDO remains committed to providing products and solutions that help scientists and researchers make a real difference in the world.
Guide: Innovative Techniques for Downstream Bioprocessing
Driven by need, innovation, and emerging regulatory guidance, the biopharmaceutical industry is adapting new downstream bioprocessing techniques. This guide discusses how scientists are utilizing Process Analytical Technology (PAT) to transform day-to-day workflows and make significant downstream process improvements.
Applications
Citations and References
- Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials, 6(12), 1078–1094.https://doi.org/10.1038/s41578-021-00358-0
- 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. https://doi.org/10.3390/molecules25132991
- 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. https://doi.org/10.1016/j.ijpharm.2005.05.032
More Information
FAQs
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.