Drug delivery systems to treat connective tissue disorders

Date:
October 8, 2020
Source:
University of Delaware
Summary:
A research team has devised tiny cargo-carrying systems many times
smaller than a human hair, made from molecules called peptides
that help provide structure for cells and tissues. The team has
reported advances in the nanoparticle design that allow them to
control the shape of the nanoparticles to allow them to better
bind to tissue in the body and stay in a particular location.



FULL STORY ========================================================================== University of Delaware Professor Kristi Kiick is leading collaborative
research to create new drug delivery systems with the potential to
improve treatment for diseases that affect connective tissues, such as osteoarthritis or rheumatoid arthritis, which is an autoimmune disease.


==========================================================================
The UD researchers have devised tiny cargo-carrying systems many times
smaller than a human hair. These systems, or carriers, are made from
molecules called peptides that help provide structure for cells and
tissues.

The research team is working to program these nanoparticle carriers
to selectively bind to degrading collagen in the body. Collagen is a
protein that helps plump up or provide structure to connective tissue -- everything from our skin to our bones, tendons and ligaments.

When collagen degrades, as a result of disease or injury, the
nanoparticles designed by the Kiick lab can attach and remain at the
injury site longer than many current treatment options. This allows
for the possibility of delivering site-specific medicines over longer
periods of time -- from days to weeks.

In one collaborative project that involves this work, Kiick is trying
to develop drug carriers that could be useful in treating osteoarthritis.

Osteoarthritis is a degenerative joint disorder characterized by
inflammation, pain and stiffness. According to the Centers for Disease
Control and Prevention, it affects 32.5 million Americans.

Early studies with Christopher Price, an associate professor in biomedical engineering, suggests that these nanoparticles can be retained in tissue
and knee joints. In other related studies, Kiick and her students have
shown that drugs can be encapsulated and retained in the nanoparticles,
until released by changes in temperature.



==========================================================================
"We are interested in learning how to release drugs that can help not just
with pain management, but also with slowing down disease progression,"
said Kiick, Blue and Gold Distinguished Professor of Materials Science
and Engineering. "It has been key that we have been able to collaborate
with the Price laboratory in this type of work." For a long time, small molecule corticosteroids have been a standard of care for managing pain
in osteoarthritic joints. Because the joint is full of thick, sticky
fluid and is under constant mechanical stress and motion, these small-
molecule drugs get expelled from the fluid around the knee pretty quickly,
in minutes.

"We are hopeful that by controlling the nanoparticle composition and structure," said Kiick, "we will be able to finely control, or tune,
the drug delivery behavior to provide longer-lasting relief for people
with inflammatory conditions, such as osteoarthritis." The paper's
key findings demonstrate the research team's ability to control the
shape of the nanoparticles, which will impact how well they can bind
to tissue in the body and stay in a particular location. The research
team also can precisely control the size of the nanoparticles, which has implications for how they might be retained at the injection site and also
how they may be used by particular cells before being removed from the
body. Finally, the paper describes some of the very fine details of how
the specific building blocks inside these peptide molecules can affect
the temperature at which those different shaped and sized nanoparticles
can be disassembled to release a medicine.

The research builds on Kiick's previous patented and patent-pending
work in this area, but she said it is collaboration with others that is
driving forward promising results. While the Kiick lab brings expertise
in creating novel materials that can be used as delivery systems; Arthi Jayaraman, Centennial Term Professor for Excellence in Research and
Education in the Department of Chemical and Biomolecular Engineering, is helping the team understand factors related to temperature sensitivity
of the delivery vehicles and to develop computational tools that can
help the research team characterize the vehicle's shape.



========================================================================== Meanwhile, Price's expertise in understanding post-traumatic
osteoarthritis has been key to developing methods to use these
nanoparticles to potentially treat disease. Price is exploring how
particular drugs and cells interact, which may inform what specific
classes of medicines are useful in treating osteoarthritis that develops following traumatic injury. The collaboration will help the Kiick lab
tailor what types of nanoparticle devices can be used to deliver these different classes of medicines.

According to Kiick, thinking big, the team could imagine loading a custom cocktail of medicines into the drug-delivering nanoparticles capable
of delivering relief over varying timescales and temperatures. The
researchers already have the right material nanostructure that can allow
this to happen; now they are exploring how to trigger the nanoparticles
to release specific medications under particular conditions.

"You could imagine injecting these encapsulated medications at the knee,"
she explained. "Then, when you want one medication to be released,
the patient could ice their knee. If another drug is needed to provide
relief over a longer time-period, heat could be applied." It could be
a really simple way to help people manage chronic conditions that cause
a lot of pain and reduce mobility. And because the treatment is local,
it could reduce side effects that can occur when drugs have to be taken
at high doses or over prolonged periods of time.

"If these delivery vehicles could reduce painful effects of
osteoarthritis, or delay when osteoarthritis symptoms emerge, there could
be important implications for improving quality of life for many people,"
Kiick said.


========================================================================== Story Source: Materials provided by University_of_Delaware. Original
written by Karen B.

Roberts. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jingya Qin, Jennifer D. Sloppy, Kristi L. Kiick. Fine structural
tuning
of the assembly of ECM peptide conjugates via slight sequence
modifications. Science Advances, 2020; 6 (41): eabd3033 DOI:
10.1126/ sciadv.abd3033 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201008142148.htm

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