The challenge in LNP production is how to manufacture lipid-based nanoparticles which exhibit strong efficacy and functionality which can be scaled from lab and/or pilot results to mass-production volumes.
The use of solvents adds another difficult step to be overcome - that of removal. This makes the entire process more complicated and time-consuming as steps are taken for solvent removal.
Our lipid nanoparticles 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 lab, pilot and full-scale vaccine production.
The technology scales linearly from the lab to production, where it is possible to produce batches on the scale of thousands of liters. Essential in the fight against sars cov-2 infection (COVID-19).
Microfluidizer® technology is a trusted solution for lipid nanoparticle production. It is easy to operate and achieves a consistent particle size with narrow distributions. Due to Microfluidics’ capabilities, cost-efficient and gentle sterile filters can be applied so small nanoparticles can pass through sterile filters without clogging or losing product and production interruptions are preventable.
Microfluidizer® processors are scalable from the lab size to full production models, all of which conform to cGMP requirements and are FDA approved processes.
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 the 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 to a pandemic situation because the LNPs can be stockpiled and only the DNA/RNA would need to be produced after the pandemic began.
Lipid nanoparticles production with an 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.
There are many different techniques for the 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 Microfluidizer® Processor to reduce their size to small uni-lamellar vesicles.
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 a 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 that 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 Microfluidizer® technology is the right solution for your vaccine development and production needs - why not come into our labs and talk to our Application Specialists - schedule a lab test today.
Advantages of Microfluidizer® Technology for creating Lipid Nanoparticles.
Customers using Microfluidizer® 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 as a seamless path for scaling up LNP production.
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 polydispersity index (PdI) was less than 0.1, which indicates high particle size uniformity.
Process 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.
Recommended downloads for manufacturing LNPs.
Microfluidics International Corporation, the manufacturer of Microfluidizer® high shear fluid processors, is a leader in the design and production of laboratory and commercial processing equipment used in the production of micro- and nano-scale materials for pharmaceutical, biotech, chemical and diverse industries.
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