Drug delivery capsule could replace injections for protein drugs
The new pill can inject large quantities of monoclonal antibodies and
other drugs into the lining of the stomach after being swallowed.

Date:
August 30, 2021
Source:
Massachusetts Institute of Technology
Summary:
Researchers have developed a capsule that can carry large protein
drugs, such as monoclonal antibodies, and inject them directly
into the lining of the stomach.



FULL STORY ==========================================================================
In recent years, scientists have developed monoclonal antibodies --
proteins that mimic the body's own immune defenses -- that can combat
a variety of diseases, including some cancers and autoimmune disorders
such as Crohn's disease. While these drugs work well, one drawback to
them is that they have to be injected.


==========================================================================
A team of MIT engineers, in collaboration with scientists from Brigham
and Women's Hospital and Novo Nordisk, is working on an alternative
delivery strategy that could make it much easier for patients to benefit
from monoclonal antibodies and other drugs that usually have to be
injected. They envision that patients could simply swallow a capsule
that carries the drug and then injects it directly into the lining of
the stomach.

"If we can make it easier for patients to take their medication, then
it is more likely that they will take it, and healthcare providers
will be more likely to adopt therapies that are known to be effective,"
says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at
Brigham and Women's Hospital.

In a study appearing today in Nature Biotechnology, the researchers demonstrated that their capsules could be used to deliver not only
monoclonal antibodies but also other large protein drugs such as insulin,
in pigs.

Traverso and Ulrik Rahbek, vice president at Novo Nordisk, are the senior authors of the paper. Former MIT graduate student Alex Abramson and Novo Nordisk scientists Morten Revsgaard Frederiksen and Andreas Vegge are
the lead authors.

Targeting the stomach Most large protein drugs can't be given orally
because enzymes in the digestive tract break them down before they
can be absorbed. Traverso and his colleagues have been working on many strategies to deliver such drugs orally, and in 2019, they developed a
capsule that could be used to inject up to 300 micrograms of insulin.



==========================================================================
That pill, about the size of a blueberry, has a high, steep dome inspired
by the leopard tortoise. Just as the tortoise is able to right itself
if it rolls onto its back, the capsule is able to orient itself so
that its needle can be injected into the lining of the stomach. In the
original version, the tip of the needle was made of compressed insulin,
which dissolved in the tissue after being injected into the stomach wall.

The new pill described in the Nature Biotechnology study maintains the
same shape, allowing the capsule to orient itself correctly once it
arrives in the stomach. However, the researchers redesigned the capsule interior so that it could be used to deliver liquid drugs, in larger
quantities -- up to 4 milligrams.

Delivering drugs in liquid form can help them reach the bloodstream
more rapidly, which is necessary for drugs like insulin and epinephrine,
which is used to treat allergic responses.

The researchers designed their device to target the stomach, rather
than later parts of the digestive tract, because the amount of time it
takes for something to reach the stomach after being swallowed is fairly uniform from person to person, Traverso says. Also, the lining of the
stomach is thick and muscular, making it possible to inject drugs while mitigating harmful side effects.

The new delivery capsule is filled with fluid and also contains an
injection needle and a plunger that helps to push the fluid out of the
capsule. Both the needle and plunger are held in place by a pellet made
of solid sugar. When the capsule enters the stomach, the humid environment causes the pellet to dissolve, pushing the needle into the stomach lining, while the plunger pushes the liquid through the needle. When the capsule
is empty, a second plunger pulls the needle back into the capsule so
that it can be safely excreted through the digestive tract.



========================================================================== Significant levels In tests in pigs, the researchers showed that
they could deliver a monoclonal antibody called adalimumab (Humira)
at levels similar to those achieved by injection. This drug is used
to treat autoimmune disorders such as inflammatory bowel disease and
rheumatoid arthritis. They also delivered a type of protein drug known
as a GLP-1 receptor agonist, which is used to treat type 2 diabetes.

"Delivery of monoclonal antibodies orally is one of the biggest challenges
we face in the field of drug delivery science," Traverso says. "From an engineering perspective, the ability to deliver monoclonal antibodies
at significant levels really transforms how we start to think about the management of these conditions." Additionally, the researchers gave
the animals capsules over several days and found that the drugs were
delivered consistently each time. They also found no signs of damage to
the stomach lining following the injections, which penetrate about 4.5 millimeters into the tissue.

The MIT team is now working with Novo Nordisk to further develop the
system.

"Although it is still early days, we believe this device has the potential
to transform treatment regimens across a range of therapeutic areas,"
Rahbek says.

"The ongoing research and development of this approach mean that several
drugs that can currently only be administered via parenteral injections (non-oral routes) might be administered orally in the future. Our
aim is to get the device into clinical trials as soon as possible." ========================================================================== Story Source: Materials provided by
Massachusetts_Institute_of_Technology. Original written by Anne
Trafton. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Abramson, A., Frederiksen, M.R., Vegge, A. et al. Oral delivery of
systemic monoclonal antibodies, peptides and small molecules
using gastric auto-injectors. Nat Biotechnol, 2021 DOI:
10.1038/s41587-021- 01024-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210830113308.htm

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