NEW NANOGEL FOR DRUG DELIVERY
Scientists are
interested in using gels to deliver drugs because they can be molded into
specific shapes and designed to release their payload over a specified time
period. However, current versions aren't always practical because must be
implanted surgically.
To help overcome that
obstacle, MIT chemical engineers have designed a new type of self-healing
hydrogel that could be injected through a syringe. Such gels, which can carry
one or two drugs at a time, could be useful for treating cancer, macular
degeneration, or heart disease, among other diseases, the researchers say.
The new gel consists
of a mesh network made of two components: nanoparticles made of polymers
entwined within strands of another polymer, such as cellulose.
"Now you have a
gel that can change shape when you apply stress to it, and then, importantly,
it can re-heal when you relax those forces. That allows you to squeeze it
through a syringe or a needle and get it into the body without surgery,"
says Mark Tibbitt, a postdoc at MIT's Koch Institute for Integrative Cancer
Research and one of the lead authors of a paper describing the gel in Nature
Communications on Feb. 19.
Koch Institute postdoc
Eric Appel is also a lead author of the paper, and the paper's senior author is
Robert Langer, the David H. Koch Institute Professor at MIT. Other authors are
postdoc Matthew Webber, undergraduate Bradley Mattix, and postdoc Omid Veiseh.
Heal thyself
Scientists have
previously constructed hydrogels for biomedical uses by forming irreversible
chemical linkages between polymers. These gels, used to make soft contact
lenses, among other applications, are tough and sturdy, but once they are
formed their shape cannot easily be altered.
The MIT team set out
to create a gel that could survive strong mechanical forces, known as shear
forces, and then reform itself. Other researchers have created such gels by
engineering proteins that self-assemble into hydrogels, but this approach
requires complex biochemical processes. The MIT team wanted to design something
simpler.
"We're working
with really simple materials," Tibbitt says. "They don't require any
advanced chemical functionalization."
The MIT approach
relies on a combination of two readily available components. One is a type of
nanoparticle formed of PEG-PLA copolymers, first developed in Langer's lab
decades ago and now commonly used to package and deliver drugs. To form a
hydrogel, the researchers mixed these particles with a polymer -- in this case,
cellulose.
Each polymer chain
forms weak bonds with many nanoparticles, producing a loosely woven lattice of
polymers and nanoparticles. Because each attachment point is fairly weak, the
bonds break apart under mechanical stress, such as when injected through a
syringe. When the shear forces are over, the polymers and nanoparticles form
new attachments with different partners, healing the gel.
Using two components
to form the gel also gives the researchers the opportunity to deliver two
different drugs at the same time. PEG-PLA nanoparticles have an inner core that
is ideally suited to carry hydrophobic small-molecule drugs, which include many
chemotherapy drugs. Meanwhile, the polymers, which exist in a watery solution,
can carry hydrophilic molecules such as proteins, including antibodies and
growth factors.
Long-term drug
delivery
In this study, the
researchers showed that the gels survived injection under the skin of mice and
successfully released two drugs, one hydrophobic and one hydrophilic, over
several days.
This type of gel
offers an important advantage over injecting a liquid solution of drug-delivery
nanoparticles: While a solution will immediately disperse throughout the body,
the gel stays in place after injection, allowing the drug to be targeted to a
specific tissue. Furthermore, the properties of each gel component can be tuned
so the drugs they carry are released at different rates, allowing them to be
tailored for different uses.
The researchers are
now looking into using the gel to deliver anti-angiogenesis drugs to treat
macular degeneration. Currently, patients receive these drugs, which cut off
the growth of blood vessels that interfere with sight, as an injection into the
eye once a month. The MIT team envisions that the new gel could be programmed
to deliver these drugs over several months, reducing the frequency of
injections.
Another potential
application for the gels is delivering drugs, such as growth factors, that
could help repair damaged heart tissue after a heart attack. The researchers
are also pursuing the possibility of using this gel to deliver cancer drugs to
kill tumor cells that get left behind after surgery. In that case, the gel
would be loaded with a chemical that lures cancer cells toward the gel, as well
as a chemotherapy drug that would kill them. This could help eliminate the
residual cancer cells that often form new tumors following surgery.
"Removing the
tumor leaves behind a cavity that you could fill with our material, which would
provide some therapeutic benefit over the long term in recruiting and killing
those cells," Appel says. "We can tailor the materials to provide us
with the drug-release profile that makes it the most effective at actually
recruiting the cells."
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