NEW DRUG DELIVERY CAPSULE MAY REPLACE INJECTIONS
Given a choice, most patients would prefer to
take a drug orally instead of getting an injection. Unfortunately, many drugs,
especially those made from large proteins, cannot be given as a pill because
they get broken down in the stomach before they can be absorbed.
To help overcome
that obstacle, researchers at MIT and Massachusetts General Hospital (MGH) have
devised a novel drug capsule coated with tiny needles that can inject drugs
directly into the lining of the stomach after the capsule is swallowed. In
animal studies, the team found that the capsule delivered insulin more
efficiently than injection under the skin, and there were no harmful side
effects as the capsule passed through the digestive system.
"This could be
a way that the patient can circumvent the need to have an infusion or
subcutaneous administration of a drug," says Giovanni Traverso, a research
fellow at MIT's Koch Institute for Integrative Cancer Research, a
gastroenterologist at MGH, and one of the lead authors of the paper, which
appears in the Journal of Pharmaceutical Sciences.
Although the researchers
tested their capsule with insulin, they anticipate that it would be most useful
for delivering biopharmaceuticals such as antibodies, which are used to treat
cancer and autoimmune disorders like arthritis and Crohn's disease. This class
of drugs, known as "biologics," also includes vaccines, recombinant
DNA, and RNA.
"The large size
of these biologic drugs makes them nonabsorbable. And before they even would be
absorbed, they're degraded in your GI tract by acids and enzymes that just eat
up the molecules and make them inactive," says Carl Schoellhammer, a
graduate student in chemical engineering and a lead author of the paper.
Safe and effective
delivery
Scientists have
tried designing microparticles and nanoparticles that can deliver biologics,
but such particles are expensive to produce and require a new version to be
engineered for each drug.
Schoellhammer,
Traverso, and their colleagues set out to design a capsule that would serve as
a platform for the delivery of a wide range of therapeutics, prevent
degradation of the drugs, and inject the payload directly into the lining of
the GI tract. Their prototype acrylic capsule, 2 centimeters long and 1
centimeter in diameter, includes a reservoir for the drug and is coated with
hollow, stainless steel needles about 5 millimeters long.
Previous studies of
accidental ingestion of sharp objects in human patients have suggested that it
could be safe to swallow a capsule coated with short needles. Because there are
no pain receptors in the GI tract, patients would not feel any pain from the
drug injection.
To test whether this
type of capsule could allow safe and effective drug delivery, the researchers
tested it in pigs, with insulin as the drug payload. It took more than a week
for the capsules to move through the entire digestive tract, and the
researchers found no traces of tissue damage, supporting the potential safety
of this novel approach.
They also found that
the microneedles successfully injected insulin into the lining of the stomach,
small intestine, and colon, causing the animals' blood glucose levels to drop.
This reduction in blood glucose was faster and larger than the drop seen when
the same amount of glucose was given by subcutaneous injection.
"The kinetics
are much better, and much faster-onset, than those seen with traditional
under-the-skin administration," Traverso says. "For molecules that
are particularly difficult to absorb, this would be a way of actually
administering them at much higher efficiency."
"This is a very
interesting approach," says Samir Mitragotri, a professor of chemical
engineering at the University of California at Santa Barbara who was not
involved in the research. "Oral delivery of drugs is a major challenge,
especially for protein drugs. There is tremendous motivation on various fronts
for finding other ways to deliver drugs without using the standard needle and
syringe."
Further optimization
This approach could
also be used to administer vaccines that normally have to be injected, the
researchers say.
The team now plans
to modify the capsule so that peristalsis, or contractions of the digestive
tract, would slowly squeeze the drug out of the capsule as it travels through
the tract. They are also working on capsules with needles made of degradable
polymers and sugar that would break off and become embedded in the gut lining,
where they would slowly disintegrate and release the drug. This would further
minimize any safety concern.
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