A team of engineers from Washington
University in St. Louis has developed a new nanoparticle generation-delivery
method that could someday vastly improve drug delivery to the brain, making it
as simple as a sniff.
"This would be a nanoparticle nasal
spray, and the delivery system could allow a therapeutic dose of medicine to
reach the brain within 30 minutes to one hour," said Ramesh Raliya,
research scientist at the School of Engineering & Applied Science.
"The blood-brain barrier protects the
brain from foreign substances in the blood that may injure the brain,"
Raliya said. "But when we need to deliver something there, getting through
that barrier is difficult and invasive. Our non-invasive technique can deliver
drugs via nanoparticles, so there's less risk and better response times."
The novel approach is based on aerosol
science and engineering principles that allow the generation of monodisperse
nanoparticles, which can deposit on upper regions of the nasal cavity via
diffusion. Working with Assistant Vice Chancellor Pratim Biswas, chair of the
Department of Energy, Environmental & Chemical Engineering and the Lucy
& Stanley Lopata Professor, Raliya developed an aerosol consisting of gold
nanoparticles of controlled size, shape and surface charge. The nanoparticles
were tagged with fluorescent markers, allowing the researchers to track their
Next, Raliya and biomedical engineering
postdoctoral fellow Debajit Saha exposed locusts' antennae to the aerosol, and
observed the nanoparticles travel from the antennas up through the olfactory
nerves. Due to their tiny size, the nanoparticles passed through the
brain-blood barrier, reaching the brain and suffusing it in a matter of
The team tested the concept in locusts
because the blood-brain barriers in the insects and humans have anatomical
similarities, and the researchers consider going through the nasal regions to
neural pathways as the optimal way to access the brain.
"The shortest and possibly the easiest
path to the brain is through your nose," said Barani Raman, associate
professor of biomedical engineering. "Your nose, the olfactory bulb and
then olfactory cortex: two relays and you've reached the cortex. The same is
true for invertebrate olfactory circuitry, although the latter is a relatively
simpler system, with supraesophageal ganglion instead of an olfactory bulb and
To determine whether or not the foreign
nanoparticles disrupted normal brain function, Saha examined the physiological
response of olfactory neurons in the locusts before and after the nanoparticle
delivery. Several hours after the nanoparticle uptake, no noticeable change in
the electrophysiological responses was detected.
"This is only a beginning of a cool
set of studies that can be performed to make nanoparticle-based drug delivery
approaches more principled," Raman said.
The next phase of research involves fusing
the gold nanoparticles with various medicines, and using ultrasound to target a
more precise dose to specific areas of the brain, which would be especially beneficial
in brain-tumor cases.
"We want to drug target delivery
within the brain using this non-invasive approach," Raliya said. "In
the case of a brain tumor, we hope to use focused ultrasound so we can guide
the particles to collect at that particular point."
University in St. Louis. " Nanoparticle research tested in locusts focuses
on new drug-delivery method. " ScienceDaily, 12 April, 2017.
參考文獻：Ramesh Raliya et al., Non-invasive aerosol delivery
and transport of gold nanoparticles to the brain. Scientific Reports, 2017. DOI: 10.1038/srep44718