They discovered that a rigid gel scaffold in lung mucus separates large, fluid-filled pores and prevents nanoparticle movement beyond individual pore boundaries. Their findings deepen our understanding of diseases of the respiratory system, notably infections, and support the development of new inhaled medications. The researchers published their findings in the renowned scientific journal Proceedings of the National Academy of Science (PNAS).
Lung mucus: Rigid, thick gel rods separating pores filled with liquid phase. Nanoparticles - for example drug nanoparticles - become stuck at these structures as though they were bars of a cage.
Foto: Schneider/Kirch et al.
Foto: Kirch et al.
Now, as part of a German Research Foundation (DFG)-funded study, pharmacists and physicists were finally able to shed light on this dilemma. Scientists from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the HZI, together with researchers from the Saarland University, the Université Paris-Diderot, and Fresenius Medical Care Germany collaborated on the study. “The mucus inside the lungs is a very special kind of gel. Its structure is very different from other gels,“ explains Claus-Michael Lehr, Professor for Biopharmacy and Pharmaceutical Technology at the Saarland University and head of the “Drug Delivery” Department at HIPS. “Normal“ gels have a microstructure that resembles a delicate spiderweb made from thin, very fine threads that enclose small pores. When viewed under the microscope, lung mucus, by comparison, looks more like a sponge, with rigid, thick gel rods separating large pores filled with liquid gel. “These scaffold proteins are called mucins,“ explains Professor Lehr. The researchers have now shown that nanoparticles become stuck at these structures as though they were bars of a cage. The explanation for why many investigations found nanoparticles in the mucus to be highly mobile is because the research was done on a nanometer scale. Inside the pores, the particles can move around completely unobstructed and only when they try to move past individual pores are they prevented from doing so by the “bars.“
“Our results are helping us to better understand the etiology of infectious diseases of the airways and how to treat them more effectively. In particular, they represent an important basis for the continued development of new inhaled medications,“ explains Professor Lehr. The newly gained insights show that it is important to consider how drugs overcome the mucus gel scaffold. Mucolytic techniques can be used where, essentially, the rods are melted such that they dissolve before the nanoparticle and, once the particle has passed, they fuse again.
One of the research tools Professor Christian Wagner and his team of experimental physicists at the Saarland University use to support their assumptions are optical tweezers: Bundled laser beams are used to grab and move the smallest particles just like you would use a regular pair of tweezers. “We can use the optical tweezers’ laser beams to measure the force that is required to move a particle within the gel. This allows us to make conclusions about the medium that the bead is moved through,“ explains Professor Wagner. “We were able to pull the bead through the liquid inside the pore at a constant force – just as we would if we were dealing with a normal gel. However, whenever the bead hits the pore’s wall, in other words the mucus’s gel rods, the laser beam is unable to move it any further,“ explains Wagner. Experiments using an atomic force microscope as well as other tests are further supporting their hypothesis: As such, iron nanoparticles were able to penetrate the “normal“ reference gel but not the lung mucus without any difficulties under the influence of a magnetic field. Structural analyses of the mucus were performed by scientists at Fresenius Medical Care Germany using a cryo-electron microscope.
The researchers expect that insights into the special structure of lung mucus will help guiding the development of a new generation of drugs to treat diseases of the airways.
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) is an HZI branch, which was founded in 2009 jointly by HZI and the University of the Saarland. HIPS researchers are concerned with the search for new drugs against infectious diseases, their optimization for human application, and determining how they can best be delivered to their target location.
The “Drug Delivery” Department studies the distribution of drugs within the body. The focus is on investigating how drugs are able to overcome biological barriers to safely reach their destination. The development of nanotransport particles constitutes an important part of the department's work.Contact:
Ph: (+49) 681-302-3039; Email: firstname.lastname@example.org
Prof. Dr. Christian Wagner (Specialty in Experimental Physics at the Saarland University) Ph: (+49) 681-302-3003, 2416; Email: email@example.com
Hint for radio journalists: You can use the broadcast codec (IP address) to conduct studio-quality phone interviews with Saarland University scientists. Interview requests should be directed to the press office (+49) 681-302-2601.
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences