MIT engineers have invented a new 3-D fabrication method that can generate a novel type of drug-carrying
particle that could allow multiple doses of a drug or vaccine to be delivered over an
extended time period with just one injection.
The new microparticles resemble tiny coffee cups that can be filled with a drug or vaccine
and then sealed with a lid.
The particles are made of a biocompatible, FDA-approved polymer that can be designed
to degrade at specific times, spilling out the contents of the “cup.”
The Researchers are very excited about this work because, for the first time, they can
create a library of tiny, encased vaccine particles, each programmed to release at a
precise, predictable time, so that people could potentially receive a single injection
that, in effect, would have multiple boosters already built into it.
This could have a significant impact on patients everywhere, especially in the developing world
where patient compliance is particularly poor.
The researchers began working on the new drug delivery particles as part of a project funded
by the Bill and Melinda Gates Foundation, which was seeking a way to deliver multiple
doses of a vaccine over a specified period of time with just one injection.
That could allow babies in developing nations, who might not see a doctor very often, to
get one injection after birth that would deliver all of the vaccines they would need during
the first one or two years of life.
Using photolithography, they created silicon molds for the cups and the lids.
Large arrays of about 2,000 molds are fit onto a glass slide, and these molds are used
to shape the PLGA cups and lids.
PLGA is a biocompatible polymer that has already been approved for use in medical devices such
as implants, sutures, and prosthetic devices.
PLGA can also be designed to degrade at different rates, allowing for the fabrication of multiple
particles that release their contents at different times.
Once the array of polymer cups has been formed, the researchers employed a custom-built, automated
dispensing system to fill each cup with a drug or vaccine.
After the cups are filled, the lids are aligned and lowered onto each cup, and the system
is heated slightly until the cup and lid fuse together, sealing the drug inside.
The Researchers developed new method called SEAL (StampEd Assembly of polymer Layers)
to align and seal the layers.
It can make structures which current 3-D printing methods cannot.
In mice, the researchers showed that particles release in sharp bursts, without prior leakage,
at 9, 20, and 41 days after injection.
They then tested particles filled with ovalbumin, a protein found in egg whites that is commonly
used to experimentally stimulate an immune response.
Using a combination of particles that released ovalbumin at 9 and 41 days after injection,
they found that a single injection of these particles was able to induce a strong immune
response that was comparable to that provoked by two conventional injections with double
the dose.
The researchers have also designed particles that can degrade and release hundreds of days
after injection.
One challenge to developing long-term vaccines based on such particles is making sure that
the encapsulated drug or vaccine remains stable at body temperature for a long period before
being released.
They are now testing these delivery particles with a variety of drugs, including existing
vaccines, such as inactivated polio vaccine, and new vaccines still in development.
They are also working on strategies to stabilize the vaccines.