for Lipid Nanoparticles (LNP)

Microfluidizer® Technology provides a scalable solution to manufacturing Lipid Nanoparticles (LNP)

Your Challenges

The challenge is how to create the right LNP which exhibits strong efficacy and functionality, but is able to be scaled up to full mass-production scale,  producing millions of doses not just lab or pilot scale production. 

The use of solvents adds another difficult step to be overcome - that of removal.  This makes the entire process more complicated and time consuming.  

Our Experience

Our decades of applications development and engineering expertise can help to deliver your product to market as quickly as possible.

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How we can help

Our technology is simple to use, achieves consistent particle sizes with narrow distributions, which increases product stability and improves downstream processes such as sterilization - both crucial for vaccine production.

The technology scales linearly from the lab to production, where it is possible to produce batches in the scale of thousands of litres.  Vital in the fight against COVID-19. 

Our Approach

Microfluidizer® processors are scalable from the lab size to full production models, all of which conform to cGMP requirements and are FDA approved processes. 

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In detail

Lipid Nanoparticles

Lipid Nanoparticles (LNPs), including various lipid-based platforms such as liposomes, nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs), are critical for the delivery of protein and amino acid type antigens.

They ensure antigens are released to the desired organs in the body and prevent uptake by Mononuclear phagocyte system (MPS).

Two approaches are commonly used when using LNPs to deliver DNA or RNA molecules - the in-situ encapsulation approach or post adsorption approach.

The former tries to incorporate DNAs or RNAs while forming the nanoparticles. A drawback is poor encapsulation efficiency and potentially reduced release rate will offset the rapid-response nature of vaccines. Furthermore, stockpiling of these DNA/RNA vaccines may not be feasible due to stability and scalability limits and hence impact readiness in response to pandemics.

The latter allows manufacturing and storing of the nanoparticle delivery systems separately from the target DNA/RNA, which are then combined prior to vaccine administration. This two-step approach is a good alternative way and ideal in responding a pandemic situation, because the LNPs can be stockpiled and only the DNA/RNA would need to be produced after the pandemic began. 

Production of LNPs with average size of approximately 100 nm is critical for transport through the body and also for sterile filtration.


To find out more about how LNPs are created using Microfluidizer Technology, please check out our webinar here.

Find out more about how  Lipid Nanoparticles are created with  microfluidizer technology  Read the blog & watch the video here

 

 

 

There are many different techniques for preparation of lipid nanoparticles.

The most common technique is demonstrated here in this 5 step process:

Step 1: The phospholipid, carrier oil and any hydrophobic actives are dissolved in a solvent. This solvent is then removed via evaporation - either by a rotor-stator at the lab-scale or by spray-drying on the production scale.

Steps 2 and 3: A buffer is added to the resulting precipitate from Step 1 and warmed and vortexed to hydrate the phospholipids.

Step 4: The antigen (or other hydrophilic actives) is added to the solution whereby large multi-layer vesicles (MLVs) are generated.

Step 5: The MLVs are processed through a Microfluidics Processor to reduce their size to small uni-lamellar vesicles.

 

LNP production steps

Ref: University of Strathclyde research

There have been recent process improvements to this classical method. If the carrier oil is a liquid or can melt in water, it is not necessary to create the solid solution of phospholipids and carrier oil. These ingredients can simply be mixed together and added to the water phase to create a pre-mix prior to processing with the Microfluidizer processor.

Furthermore, the addition of the hydrophilic antigens downstream of the LNP creation works well if the antigens can adsorb to the surface of the LNPs.

There are other methods to create LNPs using solvent precipitation methods which are suitable only for small scale production. Microfluidics can help transfer technology from solvent precipitation methods to scalable cGMP proven production methods.

 

 

If you would like to explore whether Microfluidics technology is the right solution for your vaccine development needs - why not come into our labs and talk to our Application Specialists - schedule a lab test today.

Contact us for a  demo or lab test

Advantages of Microfluidizer Technology for creating Lipid Nanoparticles

Customers using Microfluidizer® processor technology for Lipid Nanoparticle applications achieve differentiation from lab on chip technology with:

  • Scalable results from lab to production

  • The ability to produce large batch sizes in the thousands of litres scale

  • High shear processing efficiently size reducing particles

  • Uniform processing creating consistent particle size distribution

  • cGMP approved technology

  • The ability to process samples with a wide variety of concentrations of lipids

  • No need for use of solvents

Microfluidizer technology has been proven time and again over the decades

Microfluidizer technology enabled a pharmaceutical company to successfully create the appropriate nanoparticles, which were in fact liposomes, that were designed to treat carcinomas.

Small and uniform particles
The average particle size was reduced to around 40 nm. The polydisperse index (PdI) was less than 0.1, which indicates high particle size uniformity.

Scalability
The process was scaled up directly from lab scale to the production scale under the same conditions. The results obtained from the production machine was almost identical to the results produced by the lab machine.

 

If you would like advice on how to scale up your Lipid Nanoparticle formulation, please schedule a demo or lab test where we will be able to help you and prove the success of the Microfluidics technology.

Contact us for a  demo or lab test

 

 

LNP-scalability-chart2

 

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Resources

Webinar

Yvonne Perrie - Professor, Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclude, Glasgow joins Microfluidics International Corporation to discuss her liposome research performed with the Microfluidizier

WEBINAR Listen to the webinar on formulating liposomes & the importance of vesicle size control.  >click here