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Lipid Nanoparticles Development

Lipid nanoparticles (LNPs) are nanoscale particles mainly composed of lipids. Traditionally, lipid nanoparticles are known as liposomes, lipopolymers, solid lipid nanoparticles, nanostructured lipid nanoparticles, microemulsions, and nanoemulsions, and are mainly used for the release of small molecules and peptides. Recently, lipid nanoparticles have emerged as drug delivery systems for biologics, especially for COVID-19 mRNA vaccines, where lipid nanoparticles play an important role in transporting mRNA to target cells. BOC Sciences provides comprehensive one-stop customized services in the field of lipid nanoparticle development. Our expertise lies in the design, synthesis and characterization of lipid nanoparticles for a variety of applications, including drug delivery, gene therapy and diagnostic imaging.

What are Lipid Nanoparticles?

Liposome was first discovered under the microscope in 1961 by scientists A.D. Bangham and R.W. Horne. Liposome is a vesicle structure composed of lipid molecules, and its lipid bilayer forms a hydrophobic shell and an inner aqueous cavity, which has both hydrophilic and hydrophobic properties. Lipid nanoparticles are a kind of nanoparticles formed by using lipids. They are lipid vesicles with a uniform lipid core, and their essence is a solid lipid particle. In general, lipid nanoparticles are spherical vesicles composed of one (unilamellar) or multiple (multilamellar) phospholipid bilayers, usually composed of four components: cationic lipids, helper lipids, cholesterol, and PEG-lipids.

Structure of lipid nanoparticlesFig. 1. Structure of lipid nanoparticles (Current Opinion in Colloid & Interface Science. 2023, 66: 101705).

Lipid nanoparticles not only have similar physical and chemical properties to ordinary oil particle carriers, but also have greatly improved stability, absorption, distribution in vivo, and bioavailability compared with ordinary oil particle carriers. The extremely small size of the ordinary lipid particle carrier can greatly enhance the tissue permeability of the carrier. This confers good in vivo targeting of the active. At the same time, the reduction of particle size can increase the specific surface area. Within the same volume, the surface on which atoms can attach increases, and more active ingredients can be loaded. The increase in the specific surface area also greatly increases the contact area, and these active substances can be more combined with the target to exert their effects. This allows for a lower dose to be used for the same drug effect.

Lipid Nanoparticles Toxicity

Naked RNA is a negatively charged hydrophilic macromolecule that is difficult to enter cells due to the electrostatic repulsion of cell membranes and is easily degraded rapidly by ubiquitous RNases. Therefore, a protective shell is required to enter the cell. Because cell membranes are mainly composed of lipids, the use of lipid vesicles to encapsulate RNA can pass through the cell membrane and release the RNA into the cytoplasm. Therefore, the vesicle should first be a positively charged lipid capable of binding negatively charged RNA. Whereas vesicles composed of permanent cationic lipids cause cytotoxicity due to electrostatic interactions with negatively charged cell membranes, lipid structures have evolved to be positively charged molecules in response to the acidic environment of endosomes. The surface charge of lipid nanoparticles is responsible for the interaction with cell membranes and the biological environment. Because the cell membrane is negatively charged, the negatively charged lipid nanoparticles on the surface will repel the cell membrane and will not be absorbed by the cell. On the other hand, positively charged lipid nanoparticles may directly damage cell membranes, causing cytotoxicity.

Lipid nanoparticles for mRNA deliveryFig. 2. Lipid nanoparticles for mRNA delivery (Biomaterials. 2023, 301: 122279).

A commonly used approach to modulate the total charge on the surface of lipid nanoparticles is to adjust the N/P ratio, that is, the ratio of ionizable lipids (N, representing cationic amines) to nucleic acids (P, representing anionic phosphates). For example, Carrasco et al. reported that increasing the N/P ratio could increase the surface charge and encapsulation efficiency in lipid nanoparticles containing the ionizable lipid KC2. Furthermore, the introduction of permanently charged lipids into lipid nanoparticles may alter the preferential uptake propensity of organs without increasing the surface charge. With its rich knowledge in the field of lipid nanoparticle development, BOC Sciences can assist in selecting the most suitable lipid composition according to the customer's desired application, and optimize the N/P ratio and formulation to achieve enhanced stability and encapsulation efficiency and controlled release.

Our Lipid Nanoparticles Development Capabilities

TypesFeaturesApplications
LiposomesHydrophilic drugs are entrapped in the inner water phase: lipophilic drugs are entrapped in the lipid layerEarliest lipid nanoparticles applicable to multiple drugs and gene therapies
Solid Lipid Nanoparticles/Nanostructured Lipid CarriersHigh physical stability; high entrapment capacity and bioavailability; reduced fluidity to control drug releaseProcess scale-up and production of simpler drugs
Cationic Lipid NanoparticlesStabilizes nucleic acids; prolongs residence time for nuclease degradationNucleic acid drug delivery widely used in non-viral vector systems
Targeting LiposomesSurface ligands precisely target cell receptorsImprove curative effect
Stealth LiposomeAvoid being recognized by the immune system; increase circulating half-life: promote passive accumulation of drugsPEGylation technology developed from protein drugs can avoid immune response
Cubic LiposomesGood stability: controllable core size: can contain active lipidsUsed in drug delivery systems, membrane bioreactors, biosensors

Our Technology Highlights

  • Use of anionic or pegylated lipids in lipid nanoparticle formulations to reduce particle size and prevent particle fusion/aggregation
  • Adding cholesterol to lipid nanoparticle formulations or using ionizable cationic lipids to prevent cargo leakage
  • Adjusting storage temperature, buffers and pH to avoid freeze-thaw cycles
  • Antioxidants, such as α-tocopherol, or cryoprotectants, such as trehalose or sucrose, are added during storage to prevent lipid oxidation
  • Optimizing the formulation of lipid nanoparticles to achieve a near-neutral zeta potential and increasing the hydrophilicity of lipid nanoparticles to reduce serum protein opsonization

Lipid Nanoparticle Manufacturing

BOC Sciences has a state-of-the-art facility equipped with advanced technology and equipment to support the production and fabrication of lipid nanoparticles. We work on the design and synthesis of lipid nanoparticles using a range of lipid materials, including cationic lipids, phospholipids and cholesterol. Our expertise in both small-scale and large-scale production enables us to meet the needs of projects ranging from early-stage research to commercial-scale manufacturing. Additionally, we are able to incorporate active pharmaceutical ingredients (APIs), nucleic acids, or other bioactive molecules into lipid nanoparticles. Rigorous characterization tests, such as particle size analysis, zeta potential measurement, drug loading efficiency evaluation and stability studies, are also available at BOC Sciences, which guarantee the stability, bioavailability and targeted delivery of the final product. Contact BOC Sciences to discuss your lipid nanoparticle development project and benefit from our expertise in this field.

References

  1. Marité, C. et al. Review of structural design guiding the development of lipid nanoparticles for nucleic acid delivery. Current Opinion in Colloid & Interface Science. 2023, 66: 101705.
  2. Yan, Y.F. et al. Branched hydrophobic tails in lipid nanoparticles enhance mRNA delivery for cancer immunotherapy. Biomaterials. 2023, 301: 122279.

Why BOC Sciences?

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    Multi specification for academic research and industrial production

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    Strict process parameter control to ensure product quality

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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

PEGylation of Peptides
and Proteins

Reduce the Immunogenicity of Peptide/Protein Drugs

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PEG linkers For Drug

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