Research could lead to injectable gels that release medicines over time


Date:
February 4, 2021
Source:
Stanford University School of Engineering
Summary:
The researchers dissolved polymers and nanoparticles in water,
and comingled them at room temperature to solidify a Jello-like
substance that - unlike its kitchen counterpart -- did not liquify
at higher heat, such as in the body. The technique kept in balance
two thermodynamic concepts- enthalpy, which measures energy added
to or subtracted from a material, and entropy, which describes
how energy changes make a material more or less orderly at the
molecular level.



FULL STORY ==========================================================================
Gels are formed by mixing polymers into fluids to create gooey substances useful for everything from holding hair in place to enabling contact
lenses to float over the eye.


========================================================================== Researchers want to develop gels for healthcare applications by mixing
in medicinal compounds, and giving patients injections so that the gel
releases the active pharmaceutical ingredient over a period of months
to avoid weekly or daily needle sticks.

But standing in the way is a problem that's as easily understandable as
the difference between using hair gel on a beach versus in a blizzard --
heat and cold change the character of the gel.

"We can make gels with the right slow-release properties at room
temperature but once we injected them, body heat would rapidly dissolve
them and release the medicines too quickly," said Eric Appel, assistant professor of materials science and engineering.

In a paper published Feb. 2 in the journal Nature Communications,
Appel and his team detail their successful first step toward making temperature-resistant, injectable gels with a concoction designed to
cleverly bend the laws of thermodynamics.

Appel explained the science behind this rule-breaking with an analogy to
making Jello: the solid ingredients are poured into water, then heated
and stirred to mix well. As the mixture cools, the Jello solidifies as
the molecules bond together. But if the Jello is reheated, the solid reliquefies.

The Jello example illustrates the interplay between two thermodynamic
concepts -- enthalpy, which measures the energy added to or subtracted
from a material, and entropy, which describes how energy changes make
a material more or less orderly at the molecular level. Appel and his
team had to make a medicinal Jello that didn't melt, thus losing its time-release properties, when the cool solid was heated by the body.

To accomplish this, the Stanford team created a gel made of two
solid ingredients -- polymers and nanoparticles. The polymers were
long, spaghetti- like strands that have a natural propensity to get
entangled, and the nanoparticles, only 1/1000th the width of a human hair, encouraged that tendency. The researchers began by separately dissolving
the polymers and particles in water and then stirring them together. As
the commingling ingredients began to bond, the polymers wrapped tightly
around the particles.

"We call this our molecular Velcro," said first author Anthony Yu, who
did the work as a Stanford graduate student and is now a postdoctoral
scholar at MIT.

The powerful affinity between the polymers and particles squeezed
out the water molecules that had been caught between them, and as
more polymers and particles congealed, the mixture began to gel at
room temperature. Crucially, this gelling process was achieved without
adding or subtracting energy. When the researchers exposed this gel to
the body's temperature (37.5 C) it did not liquefy like ordinary gels
because the molecular Velcro effect enabled entropy and enthalpy --
orderliness and temperature change, respectively -- to remain roughly
in balance in accord with thermodynamics.

Appel said it will take more work to make injectable, time-release
gels safe for human use. While the polymers in these experiments were biocompatible, the particles were derived from polystyrene, which is
commonly used to make disposable cutlery. His lab is already trying
to make these thermodynamically- neutral gels with fully biocompatible components.

If they are successful, a time-release gel could prove valuable for
providing anti-malarial or anti-HIV treatments in under-resourced areas
where it's difficult to administer the short-acting remedies currently available.

"We are trying to make a gel that you could inject with a pin, and then
you'd have a little blob that would dissolve away very slowly for three
to six months to provide continuous therapy," Appel said. "This would
be a game-changer for fighting critical diseases around the world."

========================================================================== Story Source: Materials provided by
Stanford_University_School_of_Engineering. Original written by Tom
Abate. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Anthony C. Yu, Huada Lian, Xian Kong, Hector Lopez Hernandez,
Jian Qin,
Eric A. Appel. Physical networks from entropy-driven non-covalent
interactions. Nature Communications, 2021; 12 (1) DOI:
10.1038/s41467- 021-21024-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/02/210204144053.htm

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