Medical Design Briefs - August 2023 - 26

Drug Delivery
" With microfluidics, each drop functions as a small reactor,
such that we can get small, similar-sized, individual crystals,
which minimizes variation in drug release rate, " says
Miller. Furthermore, the crystals dissolve at a slower rate
than traditional methods, making the release of the drug
uniform over time, and increasing the duration of the drug's
effectiveness.
" We learned that the narrow variation in the drug's release
profile is really important, " explains Han. " When you add
drugs that dissolve in water, there is this bursting period where
a lot of is dissolves in the liquid at once, and not much later.
But the crystal allows this uniform, extended release, which
helps maintain the tight range of optimal concentrations that
are needed. "
" When typical antioxidants are put into water or biological
fluid, they lose their vital activity within six hours, " describes
Kong. " But the new antioxidant crystal remains bioactive for at
least two days, so we can actually extend the duration of the
drug, and also reduce the frequency with which we have to add
antioxidants to the cell culture media. This minimizes the variation
in the type of the biomolecules the stem cells are generating
and improves the reproducibility of the product, which is one of
the biggest challenges in biomanufacturing at the moment. "
Increased duration of the drug's efficacy means that stem
cell cultures can be kept out of the senescence state for longer,
which leads to a larger harvest of the needed biomolecules for
therapeutics. Miller also says this method could be used for
patient-derived stem cell treatments, where the biomolecules
from a patient's own body are used to help with various tissue
ailments, such as injuries or disease.
" When we use biomolecules from donors instead of the patient,
that can have a host effect, " explains Miller. " Ideally, we
would harvest stem cells from the patient that we're treating,
grow them in a bioreactor, and harvest those biomolecules for
that therapeutic. This works well for someone who is 20, but if
we envision an elderly patient, they're going to have a high
population of these senescence cells that are not going to be
secreting the therapeutically relevant biomolecules. If we can
pull those cells out of that state and make them behave like a
healthy cell, we can get a much larger load of therapeutically
relevant biomolecules for the patient. "
The team says that while they want to continue to improve
the biomanufacturing process, there are already many potential
uses for this methodology besides just controlled delivery of
antioxidants to stem cell cultures. Most cells experience senescence,
so this technique could be applied to other cell cultures
important in medicine and therapeutics. Furthermore, the
crystals could be used to deliver sustained and controlled levels
of antioxidants, or potentially other drugs, directly into the target
tissue of a patient.
" I think the beauty here is that this is a technology development
paper, so this can be applied to various hydrophilic drugs,
disease models, and methods applications, " says Han. " We're
showing that we can maintain a sustained release of this drug at
a relatively constant rate for an extended period of time. There
are a lot of exciting studies and directions that we can go with
this technology. "
The study is published in Advanced Functional Materials and
can be found at https://doi.org/10.1002/adfm.202302232.
This article was written by Shelby Lawson, Illinois IGB. For
more information, contact Ryan Miller, Illinois IGB, at
info-igb@illinois.edu or visit www.igb.illinois.edu.
Read the study " In-Drop Thermal Cycling
of Microcrystal Assembly for
Senescence Control (MASC) with
Minimal Variation in Efficacy. "
Confocal images of mesenchymal stem cells. The left shows the senescent cells producing unwanted biomolecules; the right shows the cells after treatment
with the antioxidant crystals. (Credit: Kong Lab/Illinois IGB)
26
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Medical Design Briefs, August 2023

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Medical Design Briefs - August 2023

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