Using Lipid Nanoparticles to Design Vaccine Delivery Systems

This article is taken from the Microfluidics blog, authored by Steve Mesite. You can read the original article here.

Lipid nanoparticles (LNPs) are the one of the most advanced pharmaceutical delivery systems. Used in recombinant protein and nucleic acid-based vaccines, they deliver the antigen safely and effectively, making them a key component of modern vaccine research. They increase the circulation time in the body and can help deliver the antigen to the target site.

With an average diameter of between 10 and 1000 nanometres, lipid nanoparticles are vesicles that include a lipid-based surfactant. For vaccine manufacturers, lipid nanoparticles allow a greater ability to customise the delivery system to determine the vaccine’s behaviour in the body.

Particle size is particularly important for lipid nanoparticles, as smaller particles allow better circulation through the body. Microfluidics worked with the University of Strathclyde to discover more about the importance of vesicle size in lipid nanoparticles. To view that webinar, click here.

Preparation of lipid nanoparticles

The diagram opposite demonstrates a common technique used to produce LNPs.  The phospholipid, carrier oil and actives are dissolved in a solvent, which is then evaporated. This precipitate has a buffer added to it and is then warmed and vortexed to hydrate the phospholipids. The antigen is then added wherein multi-layer vesicles (MLVs) are generated. This solution is processed through a Microfluidics Processor to reduce particle size to small uni-lamellar vesicles.

Credit: University of Strathclyde. Click to view.

Benefits of Lipid Nanoparticles as a Delivery System

Choosing a lipid nanoparticle delivery system yields many benefits in vaccine development. Here are just some of them:

  • Both hydrophilic and hydrophobic agents can be encapsulated together with high efficiency.
  • The lipid nanoparticles can be coated with inert and biocompatible polymers, prolonging the liposome’s circulation half-life in the body.
  • They can also be functionalised with specific ligands to change the way the vaccine behaves, and which specific cells, tissues and organs it will target.

The Effect of Electric Charge on Lipid Nanoparticles in Vaccine Efficacy

Controlling the electric charge of lipid nanoparticles is a real asset in vaccine production, allowing vaccine manufacturers to dictate how the vaccine is distributed through the body. To demonstrate this, we explored the circulation rate of four different lipid nanoparticle delivery system formulations, each with different electric charges.

Anionic formulations move away from the injection site more quickly than neutrally charged formulations. Conversely, cationic formulations remain at the injection site for much longer, which can form a depot effect: where the antigen is slowly released from the injection site.

For vaccine manufacturers, this depot effect can be helpful for delivery systems where a slow, steady release of antigen is desired. This can translate into fewer doses required to create immunity in the patient.

However, a depot effect can also be counterproductive if a high concentration of antigen in the blood serum is needed to cause immunogenicity. To achieve this, the active will need to be released and circulated as quickly as possible. Negatively charged lipid nanoparticles are the best way to achieve a quick release of the antigen.


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