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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>