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Lipid Nanoparticles

Microfluidizer® Technology provides a scalable solution for the Lipid Nanoparticles (LNPs) manufacturing process.

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.

LNPs increase the circulation time in the body and help deliver the antigen to the target site.


Achieving Homogeneous Lipid Nanoparticle Formulations

The challenge in LNP production is manufacturing lipid-based nanoparticles which exhibit strong efficacy and functionality that can not only be repeated batch-to-batch but also be scaled from lab and/or pilot results to mass-production volumes.

The use of solvents adds another difficult factor to overcome - that of removal. This makes the entire process more complicated, costly and time-consuming as steps need to be taken for solvent removal.


Technology for Manufacturing Lipid Nanoparticles

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).


Reproducible Lipid Nanoparticle Manufacturing

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.


Scalable Lipid Nanoparticle Production

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

Our dedicated team of application engineers and subject matter experts offer support through leading-edge technology and equipment expertise.

For repeatable lipid nanoparticle production batch-to-batch, Microfluidizer® technology achieves the same results from research and development to commercial volumes.



Developing LNPs

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).

For an in-depth understanding of how our technology is used in this key application, watch our webinar as HDT Bio's Dr. Darrick Carter discusses its proprietary drug delivery technology and the role Microfluidizer® processors play in addressing an efficient, scalable production solution.

Two approaches are commonly used when using LNPs to deliver DNA or RNA molecules:

In-situ encapsulation approach

This approach attempts to incorporate DNAs or RNAs while forming the nanoparticles.

A drawback to this approach is poor encapsulation efficiency and potentially reduced release rate which will offset the rapid-response nature of vaccines.

Further challenges include that DNA/RNA vaccines present stability and scalability limits. Therefore, impact readiness in response to future pandemics would be a crucial issue since stockpiling these vaccines may not be feasible.

Post absorption approach

This approach allows the manufacturing and storing of the nanoparticle delivery systems separately from the target DNA/RNA and is combined prior to vaccine administration.

This alternative two-step method is an ideal response to a pandemic situation because the LNPs can be stockpiled. Therefore, if a pandemic began, only the DNA/RNA would need to be produced.

Lipid nanoparticle production with an average size of approximately 100 nm is critical for transport through the body and also for sterile filtration.


RNA Vaccine Delivery Systems Using LNPs

For more information, view our application note on creating RNA vaccine delivery systems.

This application note summarizes a recent article comparing the in-situ encapsulation approach against the post adsorption approach of LNP manufacturing. It is concluded that the post absorption approach is highly suitable for large-scale manufacturing & responding to pandemic situations.

Download the Application Note

Preparing Lipid Nanoparticles

Amongst the many different techniques for the preparation of lipid nanoparticles, the most common is demonstrated below.

Lipid nanoparticles preparation techniques

Ref: University of Strathclyde research

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.

Step 2: A buffer is added to the resulting precipitate from Step 1.

Step 3: This is then 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. The MLVs are processed through a Microfluidizer® processor to reduce their size to small uni-lamellar vesicles.

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.

Pharmaceutical Challenges for LNP Production

Benefits of Microfluidizer® Technology for LNPs

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 capabilities
  • The ability to process samples with a wide variety of concentrations of lipids
  • No need for use of solvents

Microfluidizer® Technology for Scalable Production of Lipid Nanoparticles

This application note explores the vital role Microfluidizer® technology plays in safely producing lipid nanoparticles. The capability of the Microfluidizer® technology in producing LNPs is explored in the case study which was collaborated with Cayman Chemical Company.

Download the App Note

Proven Solutions for LNPs

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.

Watch our webinar with HDT to learn more.


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