The layers of mucus that protect sensitive tissue throughout the body have an undesirable side effect: they can also keep helpful medications away. To overcome this hurdle, Johns Hopkins researchers have found a way to coat nanoparticles with a chemical that helps them slip through this sticky barrier.
During experiments with these coated particles, the researchers also discovered that mucus layers have much larger pores than previously thought, providing a doorway that should allow larger and longer-acting doses of medicine to reach the protected tissue.
The team's findings were reported this week in the Early Online Edition of Proceedings of the National Academy of Sciences.
To get its particles past the mucus, Hanes' team studied an unlikely model: viruses. Earlier research led by Richard Cone, a professor in the Department of Biophysics at Johns Hopkins, had established that some viruses are able to make their way through the human mucus barrier. Hanes and his colleagues decided to look for a chemical coating that might mimic the characteristics of a virus.
"We found that the viruses that got through had surfaces that were attracted to water, and they had a net neutral electrical charge," said Samuel K. Lai, a Johns Hopkins chemical and biomolecular engineering doctoral student from Canada and Hong Kong who was lead author of the journal article. "We thought that if we could coat a drug-delivery nanoparticle with a chemical that had these characteristics, it might not get stuck in the mucus barrier."
To make their nanoparticles behave like viruses, the researchers coated them with polyethylene glycol, PEG, a non-toxic material commonly used in pharmaceuticals. PEG dissolves in water and is excreted harmlessly by the kidneys.
The researchers also considered the size of their nanoparticles. Previous studies indicated that even if nanoparticles did not stick to the mucus, they might have to be smaller than 55 nanometers wide to pass through the tiny openings in the human mucus mesh. (A human hair is roughly 80,000 nanometers wide.) Using high-resolution video microscopy and computer software, the researchers discovered that their PEG-coated 200-nanometer particles could slip through a barrier of human mucus.
They then conducted further tests to see how large their microscopic drug carriers could be before they got trapped in the mesh. Larger nanoparticles are more desirable because they can release greater amounts of medicine over a longer period of time. "We wanted to make the particles as large as possible," said Hanes, who also serves as director of therapeutics for the Institute for NanoBioTechnology at Johns Hopkins. "The shocking thing was how fast the particles that were 500 nanometers wide moved through the mucus mesh. The work suggests that the openings in the mucus barrier are much larger than originally expected by most. And we were also surprised to find that the larger nanoparticles (200 and 500 nanometers wide) actually moved through the mucus layer more quickly than the smaller ones (100 nanometers wide)."
This has important implications, Hanes said, because a 500-nanometer particle can be used to deliver medicine to a targeted area, released over periods of days to weeks. Larger particles also allow a wider array of drug molecules to be efficiently encapsulated. He and his colleagues believe this system has great potential in the delivery of chemotherapy, antibiotics, nucleic acids and other treatment directly to the lungs, gastrointestinal tract and cervicovaginal tract.
Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine
New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology