Tag Archives: Friedrich Schiller University Jena

German scientists battle tough mucus

A December 15, 2017 news item on ScienceDaily highlights cystic fibrosis research being done in Germany,

Around one in 3,300 children in Germany is born with Mucoviscidosis [cystic fibrosis; CF]. A characteristic of this illness is that one channel albumen on the cell surface is disturbed by mutations. Thus, the amount of water of different secretions in the body is reduced which creates a tough mucus. As a consequence, inner organs malfunction. Moreover, the mucus blocks the airways. Thus, the self regulatory function of the lung is disturbed, the mucus is colonized by bacteria and chronic infections follow. The lung is so significantly damaged that patients often die or need to have a lung transplant. The average life expectancy of a patient today is around 40 years. This is due to medical progress. Permanent treatment with inhaled antibiotics play a considerable part in this. The treatment can’t avoid the colonization by bacteria completely but it can keep it in check for a longer period of time. However, the bacteria defend themselves with a development of resistance and with the growth of so-called biofilms underneath the layer of mucus, which mostly block off the bacteria in the lower rows like a protective shield.

A complex way to the Pathogens

Scientists of the Friedrich Schiller University Jena, Germany succeeded in developing a much more efficient method to treat the airway infections which are often lethal. Crucial are nanoparticles that transport the antibiotics more efficiently to their destination….

A December 15, 2017 Friedrich Schiller University Jena press release (also on EurekAlert), which originated the news item, expands on the theme,

“Typically, the drugs are applied by inhalation in the body. Then they make a complicated way through the body to the pathogens and many of them don’t make it to their destination,” states Prof. Dr Dagmar Fischer of the chair for Pharmaceutical Technology at the University of Jena, who supervised the project together with her colleague Prof. Dr Mathias Pletz, a pulmonologist and infectious diseases physician, from the Center for Infectious Diseases and Infection Control at the Jena University Hospital. The project was supported by the Deutsche Forschungsgemeinschaft. First of all, the active particles need to have a certain size to be able to reach the deeper airways and not to bounce off somewhere else before. Ultimately, they have to penetrate the thick layer of mucus on the airways as well as the lower layers of the bacteria biofilm.

Nanoparticles travel more efficiently

To overcome the strong defense, the researchers encapsulated the active agents, like the antibiotic Tobramycin, in a polyester polymer. Thus, they created a nanoparticle which they then tested in the laboratory where they beforehand had simulated the present lung situation, in a static as well as in a dynamic state, i. e. with simulated flow movements. Therefore Pletz’s research group had developed new test systems, which are able to mimick the situation of the chronically infected CF-lung. The scientists discovered that their nanoparticle travels more easily through the sponge-like net of the mucus layer and is finally able to kill off the pathogens without any problems. Moreover, an additionally applied coating of polyethylenglycol makes it nearly invisible for the immune system. “All materials of a nanocarrier are biocompatible, biodegradable, nontoxic and therefore not dangerous for humans,” the researcher informs.

However, the Jena scientists don’t know yet exactly why their nanoparticle fights the bacteria so much more efficiently. But they want to finally get clarification in the year ahead. “We have two assumptions: Either the much more efficient transport method advances significantly larger amounts of active ingredients to the center of infection, or the nanoparticle circumvents a defense mechanism, which the bacterium has developed against the antibiotic,” the Jena Pharmacist Fischer explains. “This would mean, that we succeeded in giving back its impact to an antibiotic, which had already lost it through a development of resistance of the bacteria.”

“More specifically, we assume that bacteria from the lower layers of the biofilm transform into dormant persisters and hardly absorb any substances from outside. In this stadium, they are tolerant to most antibiotics, which only kill off self-dividing bacteria. The nanoparticles transport the antibiotics more or less against their will to the inner part of the cell, where they can unfold their impact,” Mathias Pletz adds.

Additionally, the Jena research team had to prepare the nanoparticles for the inhalation. Because at 200 nanometers the particle is too small to get into the deeper airways. “The breathing system filters out particles that are too big as well as those which are too small,” Dagmar Fischer explains. “So, we are left with a preferred window of between one and five micrometers.” The Jena researchers also have promising ideas for resolving this problem.

Coating of Nanoparticles enhances the impact of Antibiotics against Biofilms

The scientists from Jena are at this point already convinced to have found a very promising method to fight respiratory infections of patients with mucoviscidosis. Thus they may be able to contribute to a higher life expectancy of those affected. “We were able to show that the nanoparticle coating improves the impact of the antibiotics against biofilm by a factor of 1,000,” the pulmonologist and infectious diseases physician is happy to say.

It’s exciting news and I wish the researchers great success. Perhaps, one day, they will publish a paper about their work.

Sweet, sugary computer (calculator); chemistry in action

This computer is also described as sugar-based molecular computing in a June 19, 2014 news item on Nanowerk,

In a chemistry lab at the Friedrich Schiller University Jena (Germany): Prof. Dr. Alexander Schiller works at a rectangular plastic board with 384 small wells. The chemist carefully pipets some drops of sugar solution into a row of the tiny reaction vessels. As soon as the fluid has mixed with the contents of the vessels, fluorescence starts in some of the wells. What the Junior Professor for Photonic Materials does here – with his own hands – could also be called in a very simplified way, the ‘sweetest computer in the world’. The reason: the sugar molecules Schiller uses are part of a chemical sequence for information processing.

A June 19, 2014 Friedrich Schiller University Jena news release (also on EurekAlert), which originated the news item, provides an description by the lead researcher, Schiller,

Professor Schiller explains. “There is either electricity flowing between both poles of an electric conductor or there isn’t.” These potential differences are being coded as “0” and “1” and can be linked via logic gates – the Boolean operators like AND, OR, NOT. In this way, a number of different starting signals and complex circuits are possible.

These logic links however can also be realized with the help of chemical substances, as the Jena chemists were able to show. For their ‘sugar computer’ they use several components: One fluorescent dye and a so-called fluorescence quencher. “If there are both components involved, the colorant can’t display its impact and we don’t see a fluorescence signal,” Schiller says. But if sugar molecules are involved, the fluorescence quencher reacts with the sugar and thus loses its capability to suppress the fluorescence signal, which makes the dye fluorescent. Depending on whether the dye, the fluorescence quencher and the sugar are on hand to give the signal, a fluorescent signal results – “1” – or no signal – “0”.

“We link chemical reactions with computer algorithms in our system in order to process complex information,” Martin Elstner explains. “If a fluorescence signal is registered, the algorithm determines what goes into the reaction vessel next.” In this way signals are not translated and processed in a current flow, like in a computer but in a flow of matter. That their chemical processing platform works, Schiller and his staff demonstrated in the current study with the sample calculation 10 + 15. “It took our sugar computer about 40 minutes, but the result was correct,” Prof. Schiller says smiling, and clarifies: “It is not our aim to develop a chemical competition to established computer chips.” The chemist rather sees the field of application in medical diagnostics. So it is for instance conceivable to connect the chemical analysis of several parameters of blood and urine samples via the molecular logic platform for a final diagnosis and thus enable decisions for therapies.

Here’s a link to and a citation for the paper,

Sugar-based Molecular Computing by Material Implication by Martin Elstner, Jörg Axthelm, and Prof.Dr. Alexander Schiller. Angewandte Chemie International Edition DOI: 10.1002/anie.201403769 Article first published online: 12 JUN 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

One final note, Friedrich Schiller University Jena is also known as the University of Jena.