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In a Johns Hopkins chemical and
biomolecular engineering lab, Justin Hanes, an associate professor,
and doctoral student Samuel K. Lai tested coated nanoparticles
that could deliver medications through the body's sticky mucus
layers.
Using high-resolution video microscopy and computer
software, doctoral student Samuel K. Lai and Justin Hanes,
associate professor of chemical and biomolecular engineering at
Johns Hopkins, were able to track their coated nanoparticles as
the potential medication carriers made their way through a mucus
layer.
Photos: Will Kirk/JHU
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The discoveries are important because mucus
layers, which trap and help remove pathogens and other foreign
materials, can block the localized delivery of drugs to many parts of
the body, including the lungs, eyes, digestive tract and female
reproductive system. Because of these barriers, doctors often must
prescribe pills or injections that send drugs through the entire body,
an approach that can lead to unwanted side effects or doses that are
too weak to provide effective treatment.
"Mucus barriers evolved to serve a helpful purpose:
to keep things out," said Justin Hanes, an associate professor of
chemical and biomolecular engineering who supervised the research. "But
if you want to deliver medicine in a microscopic particle, they can
also keep the drugs from getting through. We've found a way to keep
helpful nanoparticles from sticking to mucus, and we learned that the
openings in the mucus 'mesh' are much larger than most people expected.
These findings set the stage for a new generation of nanomedicines
that can be delivered directly to the affected areas."
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. |
