Nucleic acid-based drugs equivalent to mRNA vaccines supply large potential for medication and are opening up new therapeutic approaches. These lively elements 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 Techniques and Design Expertise IPK and FDX Fluid Dynamix GmbH have labored collectively to develop a know-how 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 know-how for its personal good manufacturing apply (GMP) manufacturing actions.
RNA and DNA, each nucleic acids, usually are not solely present in cells; they can be parts of medicines. One widespread instance broadly recognized from the coronavirus pandemic is mRNA vaccines.
Medical professionals the world over are very hopeful about nucleic acid-based lively elements, which supply potential as therapies for ailments that had been beforehand troublesome to deal with, together with some types of most cancers. Nonetheless, safely and successfully transporting these delicate nucleic acids to the cells, the place the messages they carry may be translated into proteins, has confirmed to be a big problem to date.
A protecting envelope is required to get the delicate lively ingredient into the cells. These nanoparticles are produced utilizing fluid mixing processes. Very thorough, speedy mixing is critical to supply particles of the requisite high quality. Impinging jet mixers (also referred to 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, quicker 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 persistently excessive mixing high quality at any scale, from the lab proper as much as mass manufacturing. It has already efficiently handed checks aimed toward manufacturing of lipid and polymer nanoparticles and of nanoemulsions.
As intensive testing has proven, the blending high quality of the FDmiX know-how platform is superior to the methods which were obtainable so far, enabling manufacturing of particles at beforehand unattainable ranges of high quality.
The system can also 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 worldwide improvement and manufacturing associate to the pharmaceutical, biotech, and neutraceuticals markets, has licensed the patented FDmiX know-how and is already utilizing it.
“Human cells defend themselves towards overseas genetic materials. That’s why the mRNA lively elements 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 Expertise division at Fraunhofer IPK in Berlin.
To have the ability to produce the nanoparticles, the lively ingredient dissolved in a buffer needs to be blended with one other answer, equivalent 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 are able to produce considerably smaller and extra homogeneous particles and even modify their measurement. FDmiX lets us produce mixtures of a beforehand unattainable stage 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 primary 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 primary jet once more and pushes it to the opposite facet. This causes the primary jet to oscillate repeatedly from one facet to the opposite at a excessive frequency.
On this manner, 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 checks of standard impinging mixers (also referred to 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 checks on mRNA in lipid nanoparticles utilizing completely different mixers and stream charges, FDmiX generated smaller particles with considerably decrease measurement distribution in comparison with a T-mixer on the identical stream price,” Hein explains.
In checks, the challenge companions produced nanoparticles about 10% to twenty% smaller than these produced utilizing a T-mixer. Additionally they had considerably smaller measurement distribution and excessive encapsulation effectivity and particle integrity.
Giant portions of nanoparticles are wanted in the course of the scientific part and the following manufacturing stage. Right here as nicely, the know-how from Fraunhofer IPK and FDX Fluid Dynamix GmbH is spectacular: The 2 challenge companions developed and examined mixers for varied stress and stream charges. The smallest mixers (FDmiX XS) can work at stream charges below 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 manner can be utilized for a variety of purposes, nicely past encapsulation of mRNA and stabilization of vaccines.
For instance, this know-how can 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 might help to stop stenosis, or narrowing of the blood vessels.
Nanoparticles are additionally utilized in tumor remedy, and the molecules can also be useful in treating neurodegenerative ailments equivalent to Alzheimer’s and different types of dementia.
Supplied by Fraunhofer-Gesellschaft