Medicine masquerade: Engineer develops imitation red blood cells to
deliver lifesaving drugs

Date:
March 1, 2022
Source:
University of Arizona College of Engineering
Summary:
The body's natural filters, such as the kidney and lungs,
are designed to protect the body from foreign materials. But
they also filter out large percentages of critical drugs such
as chemotherapy. Scientists are developing a new type of drug
delivery vehicle designed to bypass these filters by imitating
the properties of a red blood cell.



FULL STORY ==========================================================================
From the liver to the kidneys to the lungs, the human body is equipped
with many levels of filters, which protect the body from harmful outside materials.

But this system also has its downsides. Critically important drugs such as chemotherapy or multiple sclerosis treatments are also foreign materials,
so the body filters out a large portion of these drugs -- up to 90%,
in some cases.


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One way scientists and physicians compensate for this is by giving
patients substantial quantities of a drug. This way, even though much
of the drug gets filtered out, enough of it gets through to get the job
done. But higher dosage levels also mean more adverse side effects. To
avoid such high dosages, another strategy is to design the vehicle
carrying the drug to target a specific destination.

"Many drug delivery vehicles fail to reach the right location in the
body, and the main reason is because our bodies have this really nice
filtering system.

So many of them end up in the liver, the kidney or the spleen," said
Minkyu Kim, assistant professor of materials science and engineering and biomedical engineering. "If we can overcome this by developing new drug delivery vehicles, it will be a significant advance." Kim is setting
out to do just that with a $600,000 CAREER Award, a National Science
Foundation award in support of early-career faculty who have the potential
to serve as academic role models in research and education. His plan is
to combine materials science, synthetic biology and multiscale mechanics
to develop a new form of drug delivery microparticle designed to bypass
the body's filtration systems.

Same Drugs, New Vehicle How do you get past a system designed
to deny entry to outsiders? You masquerade as an insider. Kim is
creating a microparticle vehicle that mimics the properties of a red
blood cell. Those cells consist of a protein- and lipid-based casing
carrying hemoglobin, the protein which transports oxygen throughout
the body. Instead of being a vehicle for hemoglobin, the microparticle
Kim designs will be a vehicle for drug particles. He will first use a well-established process to contain a drug in a microsphere core. Then,
he will add a layer of artificial proteins he develops, followed by
a lipid bilayer. Taken together, these components imitate a red blood
cell, and even enable a controlled release of the drug. It can carry
these drugs past a series of biological filters to the part of the body
where the drugs are needed.

It's as if you needed to attend an event that only admitted people driving
red cars, so you borrowed a red car from a friend. You'd get to where
you had to go, because you used a vehicle that was allowed in. Of course, building a protein structure that imitates the qualities of a red blood
cell is much more complicated than borrowing a car. Red blood cells have
a few key properties which are most important to imitate. For one, they
can squeeze through very small spaces and return to their original shape,
over and over again.

"A red blood cell is about 7 micrometers in diameter, and they go through microcapillaries, which are a lot smaller than that," said Kim, who is
also a member of the BIO5 Institute. "The cytoskeleton of a red blood
cell is made up of a well-ordered structure of proteins. When it needs
to move through a small space, that structure can be extended by protein unfolding, but once the stresses are removed, the original structure
returns. A red blood cell can do this a thousand times and continue to
show the same mechanical behavior." Red blood cells can also stay in
the body much longer than typical drug delivery vehicles.

"Right now, the fate of drug delivery vehicles is up to four weeks,
maximum," Kim said. "My goal is for these microparticles to reach the
lifespan of a red blood cell, which is about four months. And eventually,
I hope, even longer." Because red blood cells are so effective at moving through the body, some researchers have investigated the possibility of
using actual red blood cells as drug vehicles. But this requires human
blood donations, particular storage methods, and careful accounting of
blood type. This vehicle Kim plans to create could be adapted to carry
a wide variety of drugs and used in patients with any blood type.

"The goal is to develop a universal platform anyone can
start with, to engineer whatever they want," Kim said. "You
can engineer the outside. You can engineer the inside." ========================================================================== Story Source: Materials provided by University_of_Arizona_College_of_Engineering. Original written by Emily Dieckman. Note: Content may be edited for style and length.


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Link to news story: https://www.sciencedaily.com/releases/2022/03/220301152348.htm

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