The fine-tuning of mixing time may be achieved through iterative experimentation, but producing and testing real-life devices is time consuming and costly. “In general, longer mixing times give lipids more time to aggregate, leading to larger aggregates and more heterogeneous size distributions, while shorter mixing times lead to smaller nanoparticles, but with lower yield,” said Hancock.įigure 2.
The size of the LNPs (which directly affects the efficacy of these nanomedicines) is largely dependent on mixing time. Producing mRNA vaccines is a difficult task. The Challenges of Lipid Nanoparticle Production When it comes to creating the vaccine, there are additional challenges to overcome. Understanding which mixing method is best for making mRNA vaccines is an important first step. However, there are several active and passive forms of mixing that are appropriate in microfluidic devices, including chaotic mixing. Moreover, even though such devices are small, molecular diffusion is generally speaking still far too slow to achieve the desired rate of mixing. “The challenge is that with microfluidic devices in order to achieve efficient, rapid mixing, you cannot take advantage of the turbulent mixing, which is very efficient,” said Barakat. For small-batch drug manufacturing, such as that employed in drug discovery and development or for personalized medicine, microfluidic devices are employed due to their low fluid volumes. For production-scale drug manufacturing, turbulent flows are used, which rapidly mix via the cascade of large eddies breaking down into smaller and smaller eddies, which enhances the effectiveness of molecular diffusion. Image courtesy of Veryst Engineering.īarakat explained that there are two common ways that the components can be mixed to form these aggregates. A schematic detailing the production of an mRNA vaccine. “Given sufficient residence and mixing time, these components mix and self-assemble to spontaneously form aggregates.” It is these aggregates, the LNPs, that make up the mRNA vaccines that have captured public attention in recent years.įigure 1. The aqueous phase contains the mRNA, which is negatively charged, and the organic phase contains the lipids that are meant to encapsulate it,” said Barakat. “Broadly speaking, what you have is an organic phase being mixed with an aqueous phase. In a keynote talk from COMSOL Day: Pharmaceutical Applications, Matthew Hancock, a partner at Veryst, and Joseph Barakat, a senior engineer at Veryst, gave an introduction to the production of mRNA vaccines and shared how simulation can enhance the design process behind these nanomedicines. Veryst Engineering is an engineering consulting firm that specializes in the use of simulation and analysis for product design, manufacturing processes, and failure analysis. MRNA Vaccine Production: Mixing and Self-Assembly Researchers could run iterative experiments to meet these requirements, but a team from Veryst Engineering proposed that a simulation-guided design process would complement the experimental work and could ultimately save on cost and time as well as aid in finding more innovative solutions. The mRNA vaccine delivery efficacy depends on the size of the LNPs and dosing: small LNPs are better at penetrating tissue and high doses are required due to low delivery yield. In recent times, they have gained public attention for their use in mRNA vaccines, specifically. Lipid nanoparticles (LNPs) are used in a variety of pharmaceutical applications, including viral vaccines, cancer therapies, analgesics, and photodynamic therapies.
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