By Dr. Ali Fourkan
Replacing daily pills with a weekly regimen could help
patients stick to their dosing schedule
Researchers
have developed a capsule that can deliver a week's worth of HIV drugs in a
single dose. This advance could make it much easier for patients to adhere to
the strict schedule of dosing required for the drug cocktails used to fight the
virus, the researchers say.
Researchers
at MIT and Brigham and Women's Hospital have developed a capsule that can
deliver a week's worth of HIV drugs in a single dose. This advance could make
it much easier for patients to adhere to the strict schedule of dosing required
for the drug cocktails used to fight the virus, the researchers say.
The
new capsule is designed so that patients can take it just once a week, and the
drug will release gradually throughout the week. This type of delivery system
could not only improve patients' adherence to their treatment schedule but also
be used by people at risk of HIV exposure to help prevent them from becoming
infected, the researchers say.
"One
of the main barriers to treating and preventing HIV is adherence," says
Giovanni Traverso, a research affiliate at MIT's Koch Institute for Integrative
Cancer Research and a gastroenterologist and biomedical engineer at Brigham and
Women's Hospital. "The ability to make doses less frequent stands to
improve adherence and make a significant impact at the patient level."
Traverso
and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior
authors of the study, which appears in the Jan. 9 issue of Nature
Communications. MIT postdoc Ameya Kirtane and visiting scholar Omar Abouzid
are the lead authors of the paper.
Scientists
from Lyndra, a company that was launched to develop this technology, also
contributed to the study. Lyndra is now working toward performing a clinical
trial using this delivery system.
"We
are all very excited about how this new drug-delivery system can potentially
help patients with HIV/AIDS, as well as many other diseases," Langer says.
"A
pillbox in a capsule"
Although
the overall mortality rate of HIV has dropped significantly since the
introduction of antiretroviral therapies in the 1990s, there were 2.1 million
new HIV infections and 1.2 million HIV-related deaths in 2015.
Several
large clinical trials have evaluated whether antiretroviral drugs can prevent
HIV infection in healthy populations. These trials have had mixed success, and
one major obstacle to preventative treatment is the difficulty in getting
people to take the necessary pills every day.
The
MIT/BWH team believed that a drug delivery capsule they developed in 2016 might
help to address this problem. Their capsule consists of a star-shaped structure
with six arms that can be loaded with drugs, folded inward, and encased in a
smooth coating. After the capsule is swallowed, the arms unfold and gradually
release their cargo.
In
a previous study, the researchers found that these capsules could remain in the
stomach for up to two weeks, gradually releasing the malaria drug ivermectin.
The researchers then set out to adapt the capsule to deliver HIV drugs.
In
their original version, the entire star shape was made from one polymer that
both provides structural support and carries the drug payload. This made it
more difficult to design new capsules that would release drugs at varying
rates, because any changes to the polymer composition might disrupt the
capsule's structural integrity.
To
overcome that, the researchers designed a new version in which the backbone of
the star structure is still a strong polymer, but each of the six arms can be
filled with a different drug-loaded polymer. This makes it easier to design a
capsule that releases drugs at different rates.
"In
a way, it's like putting a pillbox in a capsule. Now you have chambers for
every day of the week on a single capsule," Traverso says.
Tests
in pigs showed that the capsules were able to successfully lodge in the stomach
and release three different HIV drugs over one week. The capsules are designed
so that after all of the drug is released, the capsules disintegrate into
smaller components that can pass through the digestive tract.
Preventing
infection
Working
with the Institute for Disease Modeling in Bellevue, Washington, the researchers
tried to predict how much impact a weekly drug could have on preventing HIV
infections. They calculated that going from a daily dose to a weekly dose could
improve the efficacy of HIV preventative treatment by approximately 20 percent.
When this figure was incorporated into a computer model of HIV transmission in
South Africa, the model showed that 200,000 to 800,000 new infections could be
prevented over the next 20 years.
"A
longer-acting, less invasive oral formulation could be one important part of
our future arsenal to stop the HIV/AIDS pandemic," says Anthony Fauci,
director of the National Institute of Allergy and Infectious Disease, which
partly funded the research.
"Substantial
progress has been made to advance antiretroviral therapies, enabling a person
living with HIV to achieve a nearly normal lifespan and reducing the risk of
acquiring HIV. However, lack of adherence to once-daily therapeutics for
infected individuals and pre-exposure prophylaxis (PrEP) for uninfected at-risk
people remain a key challenge. New and improved tools for HIV treatment and
prevention, along with wider implementation of novel and existing approaches,
are needed to end the HIV pandemic as we know it. Studies such as this help us
move closer to achieving this goal," Fauci says.
The
MIT/BWH team is now working on adapting this technology to other diseases that
could benefit from weekly drug dosing. Because of the way that the researchers
designed the polymer arms of the capsule, it is fairly easy to swap different drugs
in and out, they say.
"To
put other drugs onto the system is significantly easier because the core system
remains the same," Kirtane says. "All we need to do is change how
slowly or how quickly it will be released."
The
researchers are also working on capsules that could stay in the body for much
longer periods of time.
The
research was also funded by the Bill and Melinda Gates Foundation, Bill and
Melinda Gates through the Global Good Fund, the National Institutes of Health,
and the Division of Gastroenterology at Brigham and Women's Hospital.
Story
Source:
Materials provided
by Massachusetts
Institute of Technology. Original
written by Anne Trafton. Note: Content may be edited for style and
length.
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