Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lung mucus gel scaffold prevents nanoparticles from getting through

23.10.2012
Scientists at the Saarland University and the Helmholtz Centre for Infection Research (HZI) unraveled lung mucus’s physical properties

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.


Lung mucus
Foto: Kirch et al.

Joint press release by the Saarland University and the Helmholtz
Centre for Infection Research
Mucus coats our airways’ internal surfaces. The viscous gel humidifies the lungs and prevents viruses and other small particles like diesel soot from entering the body unchecked. Previously unclear was the extent to which such nanoparticles are able to move through the lungs’ mucus. Here, the research evidence was contradictory. Scientists could not explain why, in inhaled medication development, drug nanoparticles often simply got stuck in the mucus never making it to their target destination inside the lung cells.

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.

Original publication:
Julian Kirch, Andreas Schneider, Berengere Abou, Alexander Hopf, Ulrich F. Schäfer, Marc Schneider, Christian Schall, Christian Wagner und Claus Michael Lehr
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus (doi: 10.1073/pnas.0709640104)

PNAS 2012

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:
Prof. Dr. Claus Michael Lehr (Specialty in Pharmacy at the Saarland University and the Helmholtz Institute for Pharmaceutical Research Saarland, HIPS)

Ph: (+49) 681-302-3039; Email: lehr@mx.uni-saarland.de

Prof. Dr. Christian Wagner (Specialty in Experimental Physics at the Saarland University) Ph: (+49) 681-302-3003, 2416; Email: c.wagner@mx.uni-saarland.de

A free-of-charge press photo can be found at http://www.uni-saarland.de/pressefotos. Please pay attention to the official terms of use.

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.

Claudia Ehrlich | idw
Further information:
http://www.uni-saarland.de
http://www.helmholtz-hzi.de

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>