Tag Archives: mucus

German scientists battle tough mucus

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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.

Gold nanorods and mucus

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Mucus can kill. Most of us are lucky enough to produce mucus appropriate for our bodies’ needs but people who have cystic fibrosis and other kinds of lung disease suffer greatly from mucus that is too thick to pass easily through the body. An Oct. 9, 2014 Optical Society of America (OSA) news release (also on EurekAlert) ‘shines’ a light on the topic of mucus and viscosity,

Some people might consider mucus an icky bodily secretion best left wrapped in a tissue, but to a group of researchers from the University of North Carolina at Chapel Hill, snot is an endlessly fascinating subject. The team has developed a way to use gold nanoparticles and light to measure the stickiness of the slimy substance that lines our airways.  The new method could help doctors better monitor and treat lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

…

“People who are suffering from certain lung diseases have thickened mucus,” explained Amy Oldenburg, a physicist at the University of North Carolina at Chapel Hill whose research focuses on biomedical imaging systems. “In healthy adults, hair-like cell appendages called cilia line the airways and pull mucus out of the lungs and into the throat. But if the mucus is too viscous it can become trapped in the lungs, making breathing more difficult and also failing to remove pathogens that can cause chronic infections.”

Doctors can prescribe mucus-thinning drugs, but have no good way to monitor how the drugs affect the viscosity of mucus at various spots inside the body. This is where Oldenburg and her colleagues’ work may help.

The researchers placed coated gold nanorods on the surface of mucus samples and then tracked the rods’ diffusion into the mucus by illuminating the samples with laser light and analyzing the way the light bounced off the nanoparticles. The slower the nanorods diffused, the thicker the mucus. The team found this imaging method worked even when the mucus was sliding over a layer of cells—an important finding since mucus inside the human body is usually in motion.

“The ability to monitor how well mucus-thinning treatments are working in real-time may allow us to determine better treatments and tailor them for the individual,” said Oldenburg.

It will likely take five to 10 more years before the team’s mucus measuring method is tested on human patients, Oldenburg said. Gold is non-toxic, but for safety reasons the researchers would want to ensure that the gold nanorods would eventually be cleared from a patient’s system.

“This is a great example of interdisciplinary work in which optical scientists can meet a specific need in the clinic,” said Nozomi Nishimura, of Cornell University … . “As these types of optical technologies continue to make their way into medical practice, it will both expand the market for the technology as well as improve patient care.”

The team is also working on several lines of ongoing study that will some day help bring their monitoring device to the clinic. They are developing delivery methods for the gold nanorods, studying how their imaging system might be adapted to enter a patient’s airways, and further investigating how mucus flow properties differ throughout the body.

This work is being presented at:

The research team will present their work at The Optical Society’s (OSA) 98th Annual Meeting, Frontiers in Optics, being held Oct. 19-23 [2014] in Tucson, Arizona, USA.

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Presentation FTu5F.2, “Imaging Gold Nanorod Diffusion in Mucus Using Polarization Sensitive OCT,” takes place Tuesday, Oct. 21 at 4:15 p.m. MST [Mountain Standard Time] in the Tucson Ballroom, Salon A at the JW Marriott Tucson Starr Pass Resort.

People with cystic fibrosis tend to have short lives (from the US National Library of Medicine MedLine Plus webpage on cystic fibrosis),

Most children with cystic fibrosis stay in good health until they reach adulthood. They are able to take part in most activities and attend school. Many young adults with cystic fibrosis finish college or find jobs.

Lung disease eventually worsens to the point where the person is disabled. Today, the average life span for people with CF who live to adulthood is about 37 years.

Death is most often caused by lung complications.

I hope this work proves helpful.

Blood-, milk-, and mucus-powered electronics

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Researchers at Tel Aviv University ([TAU] Israel) have already begun to develop biodegradable display screens in their quest to create electronic devices powered by blood, milk, and mucus proteins found in our bodies. From the March 7, 2012 news item on Nanowerk,

… a team including Ph.D. students Elad Mentovich and Netta Hendler of TAU’s Department of Chemistry and The Center for Nanoscience and Nanotechnology, with supervisor Dr. Shachar Richter and in collaboration with Prof. Michael Gozin and his Ph.D. student Bogdan Belgorodsky, has brought together cutting-edge techniques from multiple fields of science to create protein-based transistors — semi-conductors used to power electronic devices — from organic materials found in the human body. They could become the basis of a new generation of nano-sized technologies that are both flexible and biodegradable.

The March 7, 2012 news release on the American Friend of TAU website notes some of the issues with silicon-based electronics,

One of the challenges of using silicon as a semi-conductor is that a transistor must be created with a “top down” approach. Manufacturers start with a sheet of silicon and carve it into the shape that is needed, like carving a sculpture out of a rock. This method limits the capabilities of transistors when it comes to factors such as size and flexibility.

The TAU researchers turned to biology and chemistry for a different approach to building the ideal transistor. When they applied various combinations of blood, milk, and mucus proteins to any base material, the molecules self-assembled to create a semi-conducting film on a nano-scale. In the case of blood protein, for example, the film is approximately four nanometers high. The current technology in use now is 18 nanometers, says Mentovich.

Together, the three different kinds of proteins create a complete circuit with electronic and optical capabilities, each bringing something unique to the table. Blood protein has the ability to absorb oxygen, Mentovich says, which permits the “doping” of semi-conductors with specific chemicals in order to create specific technological properties. Milk proteins, known for their strength in difficult environments, form the fibers which are the building blocks of the transistors, while the mucosal proteins have the ability to keep red, green and, blue fluorescent dyes separate, together creating the white light emission that is necessary for advanced optics.

Overall, the natural abilities of each protein give the researchers “unique control” over the resulting organic transistor, allowing adjustments for conductivity, memory storage, and fluorescence among other characteristics.

I have previously featured work on vampire (blood-powered) fuel cells and batteries  in my July 18, 2012 posting and my April 3, 2009 posting so the notion of using blood (and presumably other bodily fluids) as a source for electrical power is generating (pun intended, weak though it is) interest in many research labs.

While the researchers don’t speculate about integrating these new carbon-based devices, which are smaller and more flexible than current devices, in bodies (from the American Friends of TAU news release),

Technology is now shifting from a silicon era to a carbon era, notes Mentovich, and this new type of transistor could play a big role. Transistors built from these proteins will be ideal for smaller, flexible devices that are made out of plastic rather than silicon, which exists in wafer form that would shatter like glass if bent. The breakthrough could lead to a new range of flexible technologies, such as screens, cell phones and tablets, biosensors, and microprocessor chips.

Just as significant, because the researchers are using natural proteins to build their transistor, the products they create will be biodegradable. It’s a far more environmentally friendly technology that addresses the growing problem of electronic waste, which is overflowing landfills worldwide.

The biodegradability of these proposed devices may be a problem if they are integrated into our bodies but it is certain that this will be attempted as we continue to explore machine/flesh possibilities.