UTILISATION DES NANOPARTICULES LIPIDIQUES POUR L’ADMINISTRATION DE VACCINS
Lipid nanoparticles (LNP) are one of the most advanced pharmaceutical delivery systems. Used in vaccines based on recombinant proteins and nucleic acids, they deliver antigen safely and efficiently, making it a key component of modern vaccine research. They increase circulation time in the body and can help deliver antigen to the target site.
In this blog, we provide an overview of lipid nanoparticles, how they affect delivery systems, and explain the benefits of LNPs as a delivery system.
With an average diameter between 10 and 1000 nanometers, lipid nanoparticles are vesicles that include a lipid-based surfactant. For vaccine manufacturers, lipid nanoparticles allow a greater ability to customize the delivery system to determine the behavior of the vaccine in the body.
The effects of lipid nanoparticles on delivery systems
Preparation of lipid nanoparticles. Here are some of the properties of lipid nanoparticles that can be tailored to help vaccine effectiveness and achieve desired behaviors:
- Type of phospholipid
- Transport oil (often cholesterol)
- Surface modifiers to increase circulation time in the body and prevent particles from being destroyed by the immune system
- Type of antigen (for example, protein or RNA)
- Processing method (eg thin film method using Microfluidize® technology)
- Surface charge of particles
These inputs can affect the following properties of the final vaccine:
- Circulation time in the body
- Deposit effect
- Particle size
Particle size is especially important for lipid nanoparticles because smaller particles allow better circulation through the body. We worked with the University of Strathclyde to learn more about the importance of vesicle size in lipid nanoparticles.
The diagram below illustrates a common technique used to produce NLP. The phospholipids, the carrier oil and the active ingredients are dissolved in a solvent which is then evaporated. A buffer is added to this precipitate which is then reheated and mixed to hydrate the phospholipids. The antigen is then added in which multilayer vesicles (MLVs) are generated. This solution is processed by a Microfluidizer® processor to reduce the size of the particles into small uni-lamellar vesicles.
Image Ref: University of Strathclyde research
Microfluidics technology (Here Laboratory Microfluidizer M110p) allows to reduce the size of particles into small uni-lamellar vesicles
Advantages of lipid nanoparticles as a delivery system
The choice of a lipid nanoparticle delivery system offers many advantages in vaccine development. Here are a few:
Hydrophilic and hydrophobic agents can be encapsulated with high efficiency.
The lipid nanoparticles can be coated with inert and biocompatible polymers which prolongs the circulating half-life of the liposome in the body.
They can also be functionalized with specific ligands to modify the behavior of the vaccine and the specific cells, tissues and organs they will target.
The effect of electrical charge on lipid nanoparticles in vaccine efficacy
Controlling the electrical charge of lipid nanoparticles is a real asset in vaccine production, allowing vaccine manufacturers to dictate how the vaccine is delivered throughout the body. To demonstrate this, we explored the circulation rate of four different formulations of lipid nanoparticle delivery systems, each with different electrical charges.
Anionic formulations move away from the injection site faster than neutrally loaded formulations. Conversely, cationic formulations stay at the injection site much longer which can form a depot effect.
For vaccine manufacturers, this depot effect can be useful for delivery systems where slow and steady release of the antigen is desired. This can result in fewer doses needed to create immunity in the patient.
However, a depot effect can also be counterproductive if a high concentration of the antigen in blood serum is required to cause immunogenicity. To do this, the assets will need to be disseminated and distributed as quickly as possible. Negatively charged lipid nanoparticles are the best way to achieve rapid release of the antigen.