Nucleic acid-based medicines comparable to mRNA vaccines supply large potential for medication and are opening up new therapeutic approaches. These lively components should be enclosed inside nanoparticles to make sure that they get to the place they’re wanted contained in the physique’s cells.
The Fraunhofer Institute for Manufacturing Programs and Design Know-how IPK and FDX Fluid Dynamix GmbH have labored collectively to develop a expertise platform for the manufacturing of nanoparticles that may obtain particle high quality and stability at ranges beforehand out of attain: FDmiX, brief for Fraunhofer Dynamic Mixing Applied sciences. Swiss chemical and pharmaceutical firm Lonza has now licensed the expertise for its personal good manufacturing observe (GMP) manufacturing actions.
RNA and DNA, each nucleic acids, aren’t solely present in cells; they may also be elements of medicines. One frequent instance broadly identified from the coronavirus pandemic is mRNA vaccines.
Medical professionals the world over are very hopeful about nucleic acid-based lively components, which provide potential as therapies for illnesses that had been beforehand troublesome to deal with, together with some types of most cancers. Nevertheless, safely and successfully transporting these delicate nucleic acids to the cells, the place the messages they carry might be translated into proteins, has confirmed to be a major problem to this point.
A protecting envelope is required to get the delicate lively ingredient into the cells. These nanoparticles are produced utilizing fluid mixing processes. Very thorough, fast mixing is critical to supply particles of the requisite high quality. Impinging jet mixers (often known as T-mixers or Y-mixers) can be found for industrial-scale purposes. They permit excessive throughput, however on the expense of blending high quality.
Higher, sooner mixing
Within the Fraunhofer Dynamic Mixing Applied sciences (FDmiX) platform, Fraunhofer IPK and FDX Fluid Dynamix GmbH have managed to bridge the hole between mixing high quality and throughput. The FDmiX platform permits for constantly excessive mixing high quality at any scale, from the lab proper as much as mass manufacturing. It has already efficiently handed exams aimed toward manufacturing of lipid and polymer nanoparticles and of nanoemulsions.
As in depth testing has proven, the blending high quality of the FDmiX expertise platform is superior to the methods which were obtainable up to now, enabling manufacturing of particles at beforehand unattainable ranges of high quality.
The system can be spectacular when it comes to its scaling functionality, as encapsulation can happen with quantity streams starting from 5 ml/min to 1.5 l/min with out affecting the particle properties.
Lonza, a world growth and manufacturing companion to the pharmaceutical, biotech, and neutraceuticals markets, has licensed the patented FDmiX expertise and is already utilizing it.
“Human cells defend themselves in opposition to international genetic materials. That’s why the mRNA lively components need to be enclosed inside nanoparticles. So the particles act as a protecting envelope, encapsulating the substance till it has entered the cell contained in the physique,” says Christoph Hein, head of the Extremely- and Excessive-precision Know-how division at Fraunhofer IPK in Berlin.
To have the ability to produce the nanoparticles, the lively ingredient dissolved in a buffer must be blended with one other answer, comparable to a lipid answer. As soon as the 2 liquids have been mixed, lipid nanoparticles are shaped which in flip type a lipid envelope across the lively ingredient.
“With the FDmiX platform, we will produce considerably smaller and extra homogeneous particles and even alter their measurement. FDmiX lets us produce mixtures of a beforehand unattainable degree of homogeneity with very brief mixing occasions. That’s related as a result of the blending high quality not solely determines the standard of the nanoparticles, however in the end additionally how efficient they’re.”
Intelligent nozzle design results in homogeneously blended nanoparticles
However how can a excessive and constant mixing high quality be mixed with throughput? The centerpiece of the FDmiX platform is an OsciJet nozzle from FDX Fluid Dynamix GmbH.
Contained in the nozzle, a jet of liquid is positioned on one of many sides of the principle chamber. Earlier than leaving the nozzle, a small a part of the jet is deflected right into a facet channel. On the finish of the facet channel, it meets the principle jet once more and pushes it to the opposite facet. This causes the principle jet to oscillate constantly from one facet to the opposite at a excessive frequency.
On this approach, the jet of lipid answer oscillating by the nozzle meets the stream of the mRNA lively ingredient at a perpendicular angle, making a homogeneous combination with nanoparticles of uniform measurement.
In exams of typical impinging mixers (often known as T-mixers or Y-mixers), in contrast, the lipid answer and mRNA lively ingredient collide earlier than flowing collectively by the identical channel. This creates a dynamic vortex, leading to inhomogeneous particles of decrease high quality.
“In encapsulation exams on mRNA in lipid nanoparticles utilizing totally different mixers and movement charges, FDmiX generated smaller particles with considerably decrease measurement distribution in comparison with a T-mixer on the similar movement price,” Hein explains.
In exams, the mission companions produced nanoparticles about 10% to twenty% smaller than these produced utilizing a T-mixer. In addition they had considerably smaller measurement distribution and excessive encapsulation effectivity and particle integrity.
Massive portions of nanoparticles are wanted in the course of the medical part and the following manufacturing stage. Right here as nicely, the expertise from Fraunhofer IPK and FDX Fluid Dynamix GmbH is spectacular: The 2 mission companions developed and examined mixers for varied stress and movement charges. The smallest mixers (FDmiX XS) can work at movement charges underneath 5 milliliters per minute, whereas the biggest (FDmiX XL) can work at greater than 1.5 liters per minute.
Broad vary of purposes for FDmiX nanoparticles
The nanoparticles produced on this approach can be utilized for a variety of purposes, nicely past encapsulation of mRNA and stabilization of vaccines.
For instance, this expertise may also be utilized in cardiology for cardiac catheter coatings. When a balloon catheter is expanded throughout an examination, nanoparticles are absorbed into the arterial wall, stopping new deposits from forming there. This may also help to forestall stenosis, or narrowing of the blood vessels.
Nanoparticles are additionally utilized in tumor remedy, and the molecules can also be useful in treating neurodegenerative illnesses comparable to Alzheimer’s and different types of dementia.
Offered by Fraunhofer-Gesellschaft