The interpreter: Olivia Merkel on “nanocarriers”

There are certain scientific terms that have made it into everyday life. LMU scientists explain some of these terms here—providing not just a definition but also a brief history of their popularity.

Olivia Merkel: “Nanocarriers are designed to deliver substances to their specific destination in the body. Without nanocarriers, they would not arrive safely. Nucleic acid based drugs like the coronavirus vaccines from BioNTech or Moderna, for example, are too large to reach their target cells by simple diffusion like smaller molecules can. Free nucleic acids are also unstable and degrade too quickly in the body. Nanocarriers—chemical constructs that are usually around 100 nanometers in size—encapsulate the substances and also ensure that they are actively introduced into the cells.

mRNA-vaccines are encapsulated in lipid nanoparticles

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But how do the particles reach their target? With the method known as active targeting, the surface of the nanocarriers is modified to give them a high affinity for the target cells. The inserted peptides, proteins or antibodies dock onto special receptors on the surface of the target cells through a kind of lock-and-key principle. This allows their uptake into the cell to begin. The more specific the receptors are as part of the target cells, the more easily they can be precisely targeted with nanocarriers.

The current Covid-19 vaccines also use artificial carrier particles, and technical terms such as lipid nanoparticles or indeed nanocarriers have recently begun appearing in the popular press. In the BioNTech/Pfizer and Moderna vaccines, mRNA molecules, which are a form of nucleic acid, are encapsulated in lipid nanoparticles, added to a suspension and injected as a vaccine dose. Muscle cells absorb the particles and follow the mRNA blueprint to produce the harmless coronavirus proteins that trigger an immune reaction and thus the formation of antibodies against the virus.

In the early days there were fears that the chemical polyethylene glycol (PEG) that makes up a part of the lipid envelope could cause sensitization or even anaphylactic shock in individual cases. However, it has since been demonstrated that these PEGylated lipids cause very few tolerance problems.

When I came to LMU in 2015, my specialty was still considered somewhat exotic, but now it’s en vogue. mRNA delivery is in extremely high demand. This goes for collaborations within academia as well as many companies requesting advice and seeking collaboration. My diary is certainly pretty full at the moment. The initial boost came in 2018 with the approval of the first RNA drug encapsulated in nanoparticles. That was developed for a rare disease and therefore for a small patient population. And now, of course, with mRNA vaccines, the boom is significantly bigger. Much depends on the storage stability. The Pfizer vaccine, for example, has to be stored at very low temperatures; normal freezer temperatures are not enough. We recently filed a patent application. It demonstrates the possibility to convert nanoparticles containing RNA into powder by spray drying. Drugs prepared in this way can be easily stored for long periods of time at room temperature.”

Professor Olivia Merkel is Professor of Drug Delivery in the Department of Pharmacy at LMU.