drug delivery
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Nanodroplet drug carriers triggered by ultrasound Whether a drug is swallowed, injected, inhaled or absorbed through the skin, it ultimately diffuses to most parts of the body, including those where it isn’t needed — or where it even might cause harm. But what if the delivery could be targeted at exactly the right spot?
S
cientists from The University of
Utah have been perfecting a method that does just that, with their results published in the journal Frontiers in Molecular Biosciences. “Here we show a method to deliver drugs to specific areas of the body where they are needed,” said Matthew G Wilson, the study’s first author. “We do so using ultrasound waves, which trigger drug release from circulating nanocarriers when focused on the target. “We developed a method to produce stable nanocarriers repeatably, and identified ultrasound parameters that can activate them.” The nanocarriers are minuscule droplets, between 470 and 550 nm across, with a hollow
droplet, and form a barrier against the immune
Wilson said. “We found that droplets with a PFOB
system. The effect is much like mayonnaise, where
core, which has a boiling point of 142°C, are much
proteins from eggs form droplets of encapsulated
more stable over time.
oils, where otherwise the oil and water would separate completely.
“Despite its high boiling point, PFOB can achieve similar levels of drug release when low-
To release the drug, the researchers played
frequency ultrasound of 300 kHz is applied. The
back an ultrasound — a sound wave with a
ultrasound frequency turned out to be a critical
frequency beyond the upper limit of human
factor in our study.”
hearing — of 300 or 900 kHz. The beam of
To test for safety, the researchers injected
ultrasound can be steered across three dimensions,
a single long-tailed macaque with six doses of
to focus on a desired area within the body that
PFOB-based nanodroplets at one-week intervals,
is only a few millimetres across. The ultrasound
and monitored the evolution of a range of
is thought to cause the perfluorocarbons to
blood biomarkers for liver, kidney and immune
expand, stretching out the droplet’s shell and
response function. This experiment showed that
making it more permeable to the drug, which
the nanodroplets were well tolerated, with no
then diffuses out to the organs, tissues or cells
detectable side effects. These experiments will
where it is required.
need to be replicated in microdosing or phase 1
The researchers compared the efficiency
trials on human volunteers.
of delivery of a representative drug (the
By releasing the drug at exactly the desired
anaesthetic and sedative propofol) between three
spot in the body, this allows the total dose to
polymers have two distinct ends: a hydrophilic
different perfluorocarbons: perfluoropentane
be dramatically lower, which should minimise
one, which mixes well with watery solutions
(PFP), decafluoropentane (DFP) and
side effects. Furthermore, said senior author
like blood and which faces outward, and a
perfluorooctylbromide (PFOB). The ultrasound
Assistant Professor Jan Kubanek, the method can
hydrophobic one that doesn’t mix with water
was delivered to the nanodroplets in vitro, in 60
be applied to a variety of conditions depending
and which faces inwards.
pulses of 100 ms over one minute. The results
on the drug used.
outer shell composed of polymer molecules. These
Within the shell is an inner core of
showed that the balance between stability of the
“For psychiatric applications, localised
hydrophobic perfluorocarbons — molecules
nanodroplets and the efficiency of delivery was
delivery of propofol could be used as a diagnostic
that consist mostly of fluorine and carbon, and
optimal for PFOB cores.
tool to identify brain regions causally involved in
which are mixed with an equally hydrophobic
“Previous studies have focused on
disorders for individual patients. For more lasting
drug of interest. The shells keep the cores apart,
perfluorocarbons with low boiling points —
treatment, ketamine delivery could be a potent
preventing them from coalescing into a single
usually lower than the human body temperature,”
method to rewire neural circuits,” he concluded.
28 | LAB+LIFE SCIENTIST - Aug/Sep 2024
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