What are PEG Lipids?

Polyethylene Glycol-Lipid (PEG-Lipid) derivatives have the advantages of increasing the stability of liposomes, extending their blood circulation half-life, improving their tumor targeting efficiency, and enhancing drug efficacy. In-depth study of the effects of different PEG-lipid derivatives on the physical, chemical and biological stability of liposomes is conducive to solving the current problems of PEGylated liposomes, such as the accelerated blood clearance (ABC) phenomenon caused by repeated intravenous injection, and laying a foundation for the development of new targeted preparations.

Scheme of the PEG-lipid structureFig. 1. Scheme of the PEG-lipid structure (Bioconjug Chem. 2023, 34(6): 941-960).

PEGylated Lipid

PEG Lipids represent a versatile class of amphipathic molecules with unique properties that make them valuable tools in the fields of drug delivery, imaging, diagnostics, and biotechnology. Their ability to enhance the solubility and stability of hydrophobic molecules, as well as their stealth properties and biocompatibility, have led to their widespread adoption in a variety of applications. As research in the field of lipid-based nanotechnology continues to advance, the development of novel PEG Lipids with tailored properties and functionality is expected to drive further innovation in biomedical and biotechnological applications.

Structure of PEG Lipids

PEG Lipids are amphipathic molecules composed of hydrophilic polyethylene glycol (PEG) chains and hydrophobic lipid tails. PEG chains are composed of repeating ethylene glycol units, and the length and structure of the lipid tail can vary depending on the specific PEG Lipid molecule. The amphiphilic nature of PEG Lipids enables them to self-assemble into various nanostructures such as micelles, liposomes, and lipid bilayers in aqueous environments.

Properties of PEG Lipids

One of the key properties of PEG Lipids is their ability to enhance the solubility and stability of hydrophobic molecules in aqueous solutions. Hydrophilic PEG chains provide a steric barrier that prevents aggregation of hydrophobic molecules, thus improving their bioavailability and pharmacokinetic properties. Furthermore, the presence of PEG chains on the surface of liposomes or micelles gives them stealth properties, allowing them to evade recognition by the immune system and prolong their circulation in the body.

Synthesis of PEG Lipids

PEG Lipids can be synthesized by a variety of methods, including chemical conjugation and post-insertion techniques. In chemical conjugation, PEG chains are covalently attached to lipid tails using reactive functional groups such as carboxylic acids or amines. This approach enables precise control of the length and density of PEG chains, as well as the incorporation of functional groups for specific applications. Postinsertion techniques involve the incorporation of presynthesized PEG Lipids into preformed lipid bilayers or liposomes, providing a simpler and more versatile approach to modifying the properties of lipid-based nanostructures.

Our Lipid & PEG Support Services

BOC Sciences provides custom synthesis and manufacturing services to customers requiring custom PEG Lipids with specific properties or functionality. Our team of experienced chemists and scientists are well-versed in the latest synthetic methods and technologies, allowing us to efficiently produce high-quality PEG Lipids in large quantities. BOC Sciences' state-of-the-art facility is equipped with state-of-the-art equipment and infrastructure to support the synthesis and manufacturing of PEG Lipids at commercial scale.

Why are Liposomes PEGylated?

Liposomes are spherical closed membrane vesicles with lipid as the main structure, generally used as drug delivery carriers. It has received widespread attention because it can better change drug absorption, reduce metabolism, extend biological half-life or reduce toxicity. It has received more and more attention in the fields of delivering chemical drugs, nucleic acid drugs and antibodies. Drug distribution is mainly controlled by the properties of the carrier, not just by the physical and chemical properties of the API. Ordinary liposomes are prone to drug encapsulation leakage and liposome cleavage, and are quickly cleared by the macrophage system (RES), preventing the drug from achieving its target. Therefore, improving the liposome structure to overcome existing defects and obtain the intended application has become a process that cannot be ignored from drug delivery theory to widespread clinical application.

PEGylated lipids and RNA deliveryFig. 2. PEGylated lipids and RNA delivery (Medchemcomm. 2019, 10(3): 369-377).

The breakthrough in liposome modification came in 1987-1988. Allen et al. and Gabizon et al. inserted ganglionic monoglyceride (GM1) into the phospholipid bilayer to effectively extend the blood circulation time. Furthermore, in 1990, Blume et al. and Klibanov et al. synthesized PEG-Lipid derivatives to increase their in vivo and in vitro stability and overcome the problems of purification and synthesis, price, and immunotoxicity of GM1. In addition, the PEG structure is easy to modify and comes in various types, with low price, simple and controllable process, good biocompatibility, and easy subsequent commercialization of drugs. It is PEGs liposomes that have successfully launched doxorubicin hydrochloride liposomes in various dosage forms. At present, PEG-Lipid research has developed from simple long circulation to multifunctional long circulation, such as long circulation nanoliposomes, long circulation temperature-sensitive liposomes, pH-sensitive liposomes, etc. More in-depth study of the effects of different PEG-Lipid derivative modifications on the physical, chemical and biological stability of liposomes will help solve the current problems of PEGylated liposomes.

PEGylated Lipid for Nanoparticles

Lipid nanoparticles (LNPs) have been recognized as effective carriers for the delivery of a variety of therapeutic drugs. Currently, LNPs are attracting attention as an important component of COVID-19 mRNA vaccines, playing an important role in protecting and transporting mRNA into cells. As one of its key components, PEG-Lipid conjugates are important in defining LNP physicochemical properties and biological activities. PEGylation has proven particularly effective in prolonging the systemic circulation of LNP, thereby greatly improving its pharmacokinetics and efficiency. In addition to revealing the advantages of PEG conjugates, studies have also revealed unexpected immune responses to PEGylated nanocarriers, such as accelerated blood clearance (ABC), involving the production of anti-PEG antibodies upon initial injection, thereby initiating accelerated blood clearance upon subsequent injections clearance, and a type of hypersensitivity called complement activation-related pseudoallergy (CARPA).

PEG-Lipids Control LNP Size and Stability

PEG-lipid promotes the self-assembly of LNPs through the hydrophilic spatial barrier formed by PEG chains on the LNP surface. During LNP formation, PEG chains extend from the surface of emerging particles, and sufficient PEG-lipid accumulation in each particle prevents heterogeneous formulations. The steric PEG barrier also supports particle stability by preventing aggregation. The size of LNP must be controlled during the preparation process because it plays a decisive role in the pharmacokinetics and biodistribution of nanoparticles as well as the biodistribution, delivery efficiency, and transfection efficacy of LNP. Several studies have shown that increasing the PEG-to-lipid molar ratio can be associated with significantly smaller LNP agglomerates, independent of other lipid components. In addition, the lipid tail structure in PEG-lipids also affects the biological activity of LNPs. Since PEG Lipids are incorporated into the LNP membrane via the hydrophobic tail (alkyl/acyl chain), PEG Lipids with longer tails are less likely to separate from the LNP. Studies have reported a correlation between desorption rate and lipid tail length in vitro and in vivo.

PEG-Lipids Mediate the Indirect Targeting Ability of LNPs

In addition to affecting structural properties such as size and stability, different PEG-lipid molar ratios and compositions have a great influence on in vivo distribution and cell interaction, thereby controlling the ability of LNP and LNP-like particles to fully deliver their nucleic acid cargoes in the target cells. PEGylation is a widely used method to prevent rapid clearance of nanoparticles and increase circulation time in the body. For example, incorporation of PEG-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG-DSPE) into Doxil®, which delivers the anti-tumor drug doxorubicin (Dox), can extend circulation time. These PEG-lipids anchored on the surface of Doxil®-liposomes promote the accumulation of doxorubicin at the tumor site and reduce cardiotoxicity compared to free doxorubicin by increasing circulation time.

Our PEG-Lipid for Nanoparticles

BOC Sciences is a leading supplier of PEG & Lipids, offering a comprehensive range of products and services to meet the diverse needs of the pharmaceutical, biotechnology and research industries. We have the capability to offer a variety of PEG Lipids, including PEGylated phospholipids, PEGylated cholesterol, PEGylated fatty acids, and more. These products are available in various grades and purities to meet the specific requirements of different applications. Whether customers require off-the-shelf PEG Lipid products or custom synthesis services, BOC Sciences stands ready to provide innovative solutions that drive success and growth.

What are the Applications of PEG Lipids?

PEG Lipids have been widely used in various fields, including drug delivery, imaging, diagnostics and biotechnology.

  • In drug delivery, PEGylated liposomes and micelles are used to encapsulate hydrophobic drugs and deliver them to target tissues, improving their therapeutic efficacy and reducing systemic toxicity. The stealth properties of PEG Lipids can also exploit the enhanced permeability and retention (EPR) effect to target drug delivery to specific sites in the body, such as tumors.
  • In imaging and diagnostics, PEGylated nanoparticles are used as contrast agents in various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging. Hydrophilic PEG chains on the surface of the nanoparticles enhance their stability and biocompatibility, making them suitable for in vivo imaging applications. Additionally, PEG Lipids can be functionalized with targeting ligands or antibodies to increase the specificity and sensitivity of diagnostic tests.
  • In the field of biotechnology, PEG Lipids are used to modify the surface properties of biomaterials, such as scaffolds and nanoparticles, for tissue engineering and regenerative medicine applications. The biocompatibility and versatility of PEG Lipids make them ideal candidates for creating functionalized biomaterials that can mimic the natural extracellular matrix and promote cell adhesion, proliferation, and differentiation.

If you are interested in BOC Sciences' PEG-lipid products or services, please contact us for more information. We can offer flexible pricing options and delivery schedules to meet each customer's unique needs.


  1. Tenchov, R. et al. PEGylated Lipid Nanoparticle Formulations: Immunological Safety and Efficiency Perspective. Bioconjug Chem. 2023, 34(6): 941-960
  2. Nosova, A.S. et al. Diversity of PEGylation methods of liposomes and their influence on RNA delivery. Medchemcomm. 2019, 10(3): 369-377.

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PEGylation of Peptides and Proteins

PEGylation of Peptides
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Reduce the Immunogenicity of Peptide/Protein Drugs

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Improved Circulation Half-Life

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