Medical Design Briefs - August 2024 - 23

Targeted Drug Delivery
limit of human hearing - of 300 or 900 kH. The beam of ultrasound
can be steered across three dimensions, to focus on a
desired area within the body that is only a few millimeters
across.
The ultrasound is thought to cause the perfluorocarbons to
expand, stretching out the droplet's shell and making it more
permeable to the drug, which then diffuses out to the organs,
tissues, or cells where it is required.
The researchers compared the efficiency of delivery of a representative
drug - the anesthetic and sedative propofol - between
three different perfluorocarbons, perfluoropentane
(PFP), decafluoropentane (DFP), and perfluorooctylbromide
(PFOB). The ultrasound was delivered to the nanodroplets in
vitro, in 60 pulses of 100 milliseconds over one minute.
Reaching the Boiling Point
The results showed that the balance between stability of the
nanodroplets and the efficiency of delivery was optimal for
PFOB cores.
" Previous studies have focused on perfluorocarbons with low
boiling points - usually lower than the human body temperature.
We found that droplets with a PFOB core, which has a
boiling point of 142 °C, are much more stable over time, " explains
Wilson.
" Despite its high boiling point, PFOB can achieve similar levels
of drug release when low-frequency ultrasound of 300 kH is
applied. The ultrasound frequency turned out to be a critical
factor in our study. "
To test for safety, the researchers injected a single long-tailed
macaque with six doses of PFOB-based nanodroplets at oneweek
intervals and monitored the evolution of a range of blood
biomarkers for liver, kidney, and immune response function.
This experiment, which had been approved by University of
Utah Institutional Animal Care and Use Committee, showed
that the nanodroplets were well tolerated, with no detectable
side effects. These experiments will need to be replicated in
microdosing or Phase I trials on human volunteers.
The authors also published their protocol for the production
of the nanodroplets as open science, so that other research
groups can learn directly from their findings.
" The method we developed can be applied to any of a variety
of conditions depending on the drug used. For psychiatric applications,
localized delivery of propofol could be used as a diagnostic
tool to identify brain regions causally involved in disorders
for individual patients. For more lasting treatment,
ketamine delivery could be a potent method to rewire neural
circuits, " says Wilson's academic supervisor, Dr. Jan Kubanek,
an assistant professor at the University of Utah, and the study's
senior author.
For more information, contact Matthew G. Wilson at
matt.g.wilson@utah.edu, or visit www.utah.edu.
Read the full journal article.
Soft Implantable Polymer Balloon Enables Controlled and
Targeted Drug Delivery
The device could have implications for long-term drug delivery.
Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea
I
mplants that steadily release the right dose of a drug directly to
the target part of the body have been a major advance in drug
delivery. However, they still face some key challenges, such as
ensuring that the drug is released at a constant rate from the
moment it is implanted and ensuring that the implant is soft and
flexible enough to avoid tissue damage but tough enough not to
rupture. One particular challenge is to avoid triggering the foreign
body response, which is when the patient's body encloses
the implant in a tight capsule of tough connective tissue which
can slow the drug's release or prevent it from diffusing out.
In a paper published in Biomaterials Research, a team led by
researchers from the Daegu Gyeongbuk Institute of Science
and Technology (DGIST) in the Republic of Korea present
data on their nonbiodegradable, ultrasoft, and flexible balloon
implant for drug delivery. Their findings demonstrate
the balloon's effectiveness in delivering a model drug both in
the laboratory setting and in animal models.
The balloon consists of two halves. One is made of a singlelayer
of a rubbery silicone-based polymer called polydimethylsiloxane,
and the other is a two-layer combination of polydimethylsiloxane
on the outside and the non-permeable polymer
Medical Design Briefs, August 2024
Prof. Sohee Kim's research team has successfully developed an ultrasoft and flexible
balloon-type implantable device for long-term drug delivery at the target site of implantation.
(Credit: DGIST)
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Medical Design Briefs - August 2024

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