Nucleic acid-based medicines reminiscent of mRNA vaccines provide large potential for drugs and are opening up new therapeutic approaches. These energetic substances 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 Methods 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, quick 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, aren’t solely present in cells; they may also be parts 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 energetic substances, which provide potential as therapies for ailments that had been beforehand tough 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 might be translated into proteins, has confirmed to be a big problem up to now.
A protecting envelope is required to get the delicate energetic 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 (often known as T-mixers or Y-mixers) can be found for industrial-scale functions. 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 constantly excessive mixing high quality at any scale, from the lab proper as much as mass manufacturing. It has already efficiently handed exams geared 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 have been out there so far, 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 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 in opposition to overseas genetic materials. That’s why the mRNA energetic substances should 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 energetic ingredient dissolved in a buffer must be combined with one other resolution, reminiscent of a lipid resolution. As soon as the 2 liquids have been mixed, lipid nanoparticles are fashioned which in flip kind a lipid envelope across the energetic ingredient.
“With the FDmiX platform, we are able to produce considerably smaller and extra homogeneous particles and even modify their dimension. FDmiX lets us produce mixtures of a beforehand unattainable stage of homogeneity with very quick mixing instances. That’s related as a result of the blending high quality not solely determines the standard of the nanoparticles, however finally additionally how efficient they’re.”
Intelligent nozzle design results in homogeneously combined 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 aspect channel. On the finish of the aspect channel, it meets the principle jet once more and pushes it to the opposite aspect. This causes the principle jet to oscillate repeatedly from one aspect to the opposite at a excessive frequency.
On this approach, the jet of lipid resolution oscillating by means of the nozzle meets the stream of the mRNA energetic ingredient at a perpendicular angle, making a homogeneous combination with nanoparticles of uniform dimension.
In exams of standard impinging mixers (often known as T-mixers or Y-mixers), against this, the lipid resolution and mRNA energetic ingredient collide earlier than flowing collectively by means of 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 dimension distribution in comparison with a T-mixer on the similar movement charge,” Hein explains.
In exams, the venture companions produced nanoparticles about 10% to twenty% smaller than these produced utilizing a T-mixer. Additionally they had considerably smaller dimension distribution and excessive encapsulation effectivity and particle integrity.
Massive portions of nanoparticles are wanted in the course of the scientific section and the next manufacturing stage. Right here as properly, the know-how from Fraunhofer IPK and FDX Fluid Dynamix GmbH is spectacular: The 2 venture companions developed and examined mixers for varied strain and movement charges. The smallest mixers (FDmiX XS) can work at movement charges underneath 5 milliliters per minute, whereas the most important (FDmiX XL) can work at greater than 1.5 liters per minute.
Broad vary of functions for FDmiX nanoparticles
The nanoparticles produced on this approach can be utilized for a variety of functions, properly past encapsulation of mRNA and stabilization of vaccines.
For instance, this know-how 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 help to stop stenosis, or narrowing of the blood vessels.
Nanoparticles are additionally utilized in tumor remedy, and the molecules may additionally be useful in treating neurodegenerative ailments reminiscent of Alzheimer’s and different types of dementia.
Offered by Fraunhofer-Gesellschaft
