PEG & Lipid Nanoparticles Solutions

Lipid nanoparticles (LNPs) are one of the important technologies in lipid carrier drug delivery systems and have become an important development in nucleic acid-based therapeutic drugs. Nucleic acids encapsulated in lipid nanoparticles are protected from enzymatic degradation during delivery and are efficiently delivered into cells. In the cell, the contents of the vector particles are released and translated into therapeutic proteins. Given the huge revolutionary potential of LNPs for nucleic acid-based therapeutics, a new wave of researchers is pursuing more targeted applications based on LNPs.

Structure of lipid nanoparticle-nucleic acid carrierFig. 1. Structure of lipid nanoparticle-nucleic acid carrier (ACS Nano. 2021, 15: 16982-17015).

Characteristics of Lipid Nanoparticles

LNPs are usually spherical with an average diameter between 10 and 1000 nm. They consist of a lipid core that dissolves lipophilic molecules and a surfactant layer that stabilizes the particles and protects the nucleic acid payload. The lipid core can be solid or liquid, depending on the type and composition of the lipid used. The surfactant layer can be composed of various biomembrane lipids, such as phospholipids, cholesterol, bile salts, or sterols. Optionally, LNPs can also have targeting molecules, such as antibodies or peptides, attached to their surface to enhance their specificity and uptake by certain cells. The table below summarizes some of the advantages and disadvantages of LNPs compared to other nanodrug delivery systems:

High nucleic acid encapsulation rate and strong transfection abilityComplex formulation processes and optimization
Improve penetration into tissues and cellsPotential toxicity and immunogenicity of certain lipids or surfactants
Lower cytotoxicity and immunogenicity compared to viral vectorsLimited stability and shelf life
Versatile, customizable for different nucleic acid types and applicationsMay interfere with endogenous lipid metabolism

Lipid Nanoparticles for mRNA Delivery

LNPs can be used to encapsulate mRNA to avoid extracellular degradation of the mRNA and promote its uptake by cells and release into the cytoplasm. Lipid components include, but are not limited to, ionizable/cationic lipids, auxiliary lipids (such as neutral lipids and/or cholesterol) and PEG lipids. The emergence of LNP is a milestone in the development of RNA therapy, successfully solving the problems of protecting and delivering RNA. Currently, both viral and non-viral based vectors have been developed for RNA delivery. Among them, virus-based vectors mainly include retroviral vectors, lentiviral vectors, adenoviral vectors and poxvirus vectors. Compared with viral vectors, non-viral vectors (such as protamine complexes, cationic liposomes and lipid-, polymer- or lipid/polymer-based nanoparticles, etc.) exhibit better flexibility and safety. Due to its relatively easy and scalable production method, LNP has been used in cutting-edge mRNA vaccine candidates and widely used new coronavirus vaccines.

Schematic representation of the five categories of lipid-based nanoparticlesFig. 2. Schematic representation of the five categories of lipid-based nanoparticles (Vaccines. 2021, 9: 359).

The preparation of LNPs relies on self-assembly ability, that is, the lipid components spontaneously organize into nanostructured entities through intermolecular interactions. In the mRNA vaccine, negatively charged mRNA and positively charged ionizable/cationic lipids are combined through electrostatic interactions, and then assembled through hydrophobic interactions and van der Waals interactions between lipid components to form mRNA-LNP complex. This process is a key step in the production process from purified mRNA (stock solution) to finished product (preparation), involving lipid preparation or screening, mRNA encapsulation/loading, purification and other processes.

Our LNPs Drug Delivery Strategies

BOC Sciences' PEG lipid nanoparticle solutions are designed for efficient, targeted delivery of drugs to specific cells or tissues in the body. This solution uses specific PEG-modified lipids that are biocompatible and provide excellent stability. Our PEG lipid nanoparticles can encapsulate various types of drugs, including small molecules, peptides, proteins and nucleic acids. In addition, BOC Sciences offers customization options for PEG lipid nanoparticles, allowing for the incorporation of different lipids, PEGylation densities, and drug loading capabilities. This flexibility enables optimization of formulations for specific drug candidates and therapeutic applications. Our PEG lipid nanocarrier support capabilities include:

  • Modify the composition of lipids or surfactants. Our LNPs can be designed with different types and proportions of lipids or surfactants to optimize the physicochemical properties of LNPs, such as size, charge, stability, encapsulation efficiency and release kinetics. They can also be modified with biocompatible or biodegradable lipids or surfactants to reduce their toxicity or immunogenicity.
  • Targeting molecule attachability. Our LNPs can be functionalized with ligands such as antibodies, peptides, aptamers or carbohydrates. These ligands can bind to specific receptors or antigens on the surface of target cells or tissues, which can enhance the specificity, uptake, and intracellular delivery of LNPs.
  • Responsiveness to external stimuli. Our LNPs can respond to various external stimuli, such as light, temperature, pH, magnetic field or ultrasound, which can trigger the release of nucleic acid payloads at desired sites, thereby improving LNPs release control and efficacy.
  • Systematic pre-formulation studies. Before entering clinical trials, we can evaluate the physical and chemical properties, biological interactions, pharmacokinetic characteristics and safety issues of LNPs. This helps determine optimal formulation parameters, predict potential challenges, and optimize the scale-up process.

Our LNPs Preparation Technologies

As a strategy to improve targeting capabilities, PEGylated LNPs can reduce particle clearance from the blood, thereby increasing particle retention in tissues and uptake in targeted tissues/organs. Studies have shown that PEG-modified anionic liposomes have a higher retention rate in lymph nodes compared with bare liposomes. In terms of PEG length, shorter PEG chains showed higher retention in lymph nodes than long PEG-modified liposomes. In terms of PEG structure, the use of linear or branched PEG chains can significantly improve the targeting behavior and transfection ability of LNPs.

Lipid Preparation or Screening

The source and purity of selected lipids should be characterized to ensure that potential exogenous factors are removed or controlled. The ratio of lipids is adjusted to change the physicochemical properties of LNPs, such as particle size, morphology, encapsulation efficiency, and surface charge, to better adapt to the inoculated tissue. The four commonly used lipid components include ionizable cationic lipids, PEGylated lipids, neutral lipids and cholesterol. Among them, ionizable cationic lipids are the most critical and are a decisive factor affecting drug delivery and transfection efficiency. PEGylated lipids are located on the surface of lipid nanoparticles and their content determines the size of the particles. PEGylated lipids are mainly used to improve the hydrophilicity of LNP, avoid its rapid clearance by the immune system, prevent particle aggregation, and increase stability.

Drug Encapsulation or Loading

At present, the synthesis of most LNPs is mainly based on the principle of self-assembly. The preparation principle of LNP is mainly to form a complex through rapid mixing and encapsulation of two-phase solutions. First, the original solutions of four lipids and purified drugs (such as mRNA) need to be dissolved in organic phase solution and acidic aqueous buffer respectively. Subsequently, the two-phase solutions are rapidly mixed in appropriate proportions. In this process, the acidic solution will cause the ionizable lipids in the lipids to ionize and become positively charged, thereby achieving effective encapsulation by combining with negatively charged mRNA. At the same time, as the ethanol phase solution is diluted, the solubility of the lipids continues to decrease and gradually precipitates and solidifies, thereby forming lipid particles encapsulating the mRNA in the aqueous phase solution.

Complex Purification

After the drug molecules are encapsulated, tangential flow filtration (TFF) is required for purification. The purpose is to remove unencapsulated drug molecules, free polymers, lipid materials, and lipid solvents. During this process, an ultrafiltration membrane with an appropriate molecular weight cutoff (MWCO) is usually selected to ensure that the drug-LNP complex cannot pass through the filter membrane. In addition, sterilizing filtration is an important step to ensure the sterility of vaccine preparations. Through sterilizing grade filters, bacteria and other microorganisms, contaminants and impurities are trapped in the filter and discarded.

Excipients for Lipid Nanoparticles


Lipid Nanoparticles Development Services

In addition to providing PEG solutions for LNPs, BOC Sciences also provides LNP development services. We have capabilities to provide development and optimization of lipid formulations for drug delivery. We have a wide range of lipids to choose from, including cationic, anionic and neutral lipids. Our expert team generally optimizes LNPs formulas based on customer needs, including adjusting lipid components, optimizing drug-to-lipid ratio, modifying production processes, etc., to ensure that the required drug loading, encapsulation efficiency and stability are achieved. Whether you are interested in our PEG solutions or our lipid development, we do our best to provide you with the best service. Contact us for details on our services.


  1. Zhou, Q.Q. et al. Lipid Nanoparticles-From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS Nano. 2021, 15: 16982-17015.
  2. Thi, T.T.H. et al. Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines. Vaccines. 2021, 9: 359.

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BOC Sciences supplies a unique variety of PEG derivatives and functional PEG polymers. Our products offer the most diverse collection of reactivity, ready-to-use functionality, and molecular weight options that you will not find anywhere else.

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PEGylation of Peptides and Proteins

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