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In case of antibiotic resistance, treat cystic fibrosis with nanoparticles


Cystic fibrosis: Overcoming antibiotic resistance through nanoparticles

Cystic fibrosis is a congenital metabolic disorder. In Germany alone, around 8,000 people suffer from the incurable disease, especially children and young adults. Respiratory infections are among the most common complications. Researchers have now succeeded in developing a method to treat the often fatal respiratory infections. The focus is on nanoparticles that better bring antibiotics to their destination.

Around 8,000 cystic fibrosis patients in Germany

According to health experts, up to 8,000 patients with cystic fibrosis live in Germany. About one in 3,300 children in Germany are born each year with the previously incurable metabolic disease. An early diagnosis and a therapy that is started early can help to significantly improve the quality of life and life expectancy of cystic fibrosis patients. To achieve this, the metabolic disorder test was integrated into the newborn screening. Children with cystic fibrosis in particular can often be treated well. Doctors at the University of Jena fight cystic fibrosis with nanoparticles.

Self-cleaning function of the lungs is disturbed

In cystic fibrosis (also cystic fibrosis, CF), a channel protein on the cell surface is disturbed by mutations.

This lowers the water content of various secretions in the body - it creates a tough mucus, reports the Friedrich Schiller University Jena in a message published by the Science Information Service (idw).

Malfunctions in internal organs are the result. In addition, the mucus clogs the airways. This not only disrupts the self-cleaning function of the lungs, but also causes the mucus to colonize with bacteria.

As a result, chronic infections develop. The lungs are severely damaged, which often leads to patient death or a transplant.

Thanks to medical advances, the average life expectancy of sufferers today is around 40 years.

Long-term treatments with inhaled antibiotics play an important part in this. They do not prevent bacterial colonization, but at least keep them at bay for a longer period.

However, the bacteria fight back through the development of resistance and the formation of so-called biofilms in and under the mucus layer, which primarily shield the bacteria in the lower rows like a protective shield.

Complicated way to the pathogens

Researchers at the Friedrich Schiller University in Jena have now succeeded in developing a far more efficient method to treat the often fatal respiratory infections. The focus is on nanoparticles that better bring antibiotics to their destination.

"As a rule, the medication gets into the body through inhalation and then travels a complicated way to the pathogens, many of which fall by the wayside," explains Prof. Dr. Dagmar Fischer from the Chair of Pharmaceutical Technology at the University of Jena, who led the project together with her colleague Prof. Mathias Pletz from the Center for Infectious Medicine and Hospital Hygiene at the University Hospital Jena.

The active ingredient particles must first have a certain size in order to get into the deeper respiratory tract and not ricochet off somewhere beforehand.

After all, they have to penetrate both the thick layer of mucus on the airways and the lower layers of the bacterial biofilm.

Nanoparticles reach their goal more easily

In order to overcome the concentrated resistance, the researchers encapsulated active ingredients, such as the antibiotic tobramycin, in a polyester polymer.

They tested the resulting nanoparticle in the laboratory, where they had previously simulated the existing lung situation - both in the static and in the dynamic state, i.e. with simulated flow movements.

For this purpose, Pletz’s working group had developed new test systems that can better represent the situation in the lungs.

The scientists found that their nanoparticle can get through the sponge-like network of the mucus layer more easily than the pure active ingredient and ultimately easily kill the pathogens.

An additional coating made of polyethylene glycol also makes it almost invisible to the immune system. "All of the nanocarrier materials are also biocompatible, biodegradable, non-toxic and therefore harmless to humans," says Fischer.

Give an antibiotic back its effects

The scientists in Jena do not yet know exactly why your nanoparticles fight the bacteria so effectively. But they want to finally uncover that in the coming year.

"We have two assumptions: Either the much more efficient transport method delivers significantly more active ingredient to the source of the infection or the nanoparticle overcomes a defense mechanism that the bacterium has developed against the antibiotic," explains the Jena-based pharmacist.

"The latter would mean that we were able to use a nanoparticle to give an antibiotic back its effects that it actually lost due to bacterial resistance."

“Specifically, we suspect that bacteria from the lower layers of the biofilm fall into a kind of frozen winter and hardly absorb any substances from outside. At this stage, they are unassailable to most antibiotics that only kill dividing bacteria. The nanoparticles transport the antibiotics, so to speak, against the will of the bacteria into the interior of the cell, where they can develop their effects, ”adds Mathias Pletz.

Fight respiratory infections more efficiently in cystic fibrosis patients

In addition, the Jena research team still has to prepare the nanoparticles for inhalation. Because with 200 nanometers the particle is too small to get into the deeper respiratory tract.

"The breathing system filters out particles that are both too large and too small," explains Fischer. "This leaves us with a preferred window between one and five micrometers." The Jena researchers already have promising solutions for this problem.

Based on the research results available at this point in time, the Jena research team is convinced that they have found an extremely promising method of combating respiratory infections in cystic fibrosis patients more efficiently and thus possibly contributing to a higher life expectancy of the sick.

"We were able to show that nanoparticle packaging increases the effectiveness of antibiotics against biofilms by a factor of 1,000," says the infectious disease specialist. (ad)

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Video: CF Foundation. How Gene Editing Could Be Used for CF (October 2021).