A thin strip that dissolves in the mouth like a popular
breath freshener could someday provide life-saving
rotavirus vaccine to infants in impoverished areas. The
innovative drug-delivery system was developed by Johns
Hopkins undergraduate
biomedical engineering students.
During a two-semester course, the seven-student team
fabricated a thin film that would melt quickly in a baby's
mouth, prompting the child to swallow the vaccine. The
dissolved medication is coated with a material to protect
it in the child's stomach and would release the vaccine in
the small intestine, where it would trigger an immune
response to prevent a rotavirus infection.
Rotavirus is a common cause of severe diarrhea and
vomiting in children, leading to about 600,000 deaths
annually. The novel drug-delivery system is needed because
most of these deaths occur in developing nations, where
medical services to treat intestinal distress are not
widely available. Vaccine to prevent rotavirus is currently
produced in a liquid or freeze-dried form that must be
chilled for transport and storage, making it very expensive
for use in impoverished areas. In addition, newborns
sometimes spit out the liquid, a problem that is less
likely to occur with a strip that sticks to and dissolves
on the tongue in less than a minute.
To address the drawbacks of the liquid vaccine, the
students developed a thin film delivery system that would
be easy to store and transport and would not require
refrigeration. Although further refinement is needed to
maintain the viability of the vaccine, the delivery system
itself appears sound, and the Johns Hopkins Office of
Technology Transfer has applied for a provisional patent.
"Because the strips are in a solid form, they would
cost much less to store and transport than the liquid
vaccine," said Hai-Quan Mao, the team's Johns Hopkins
faculty adviser. "We wanted this to be as simple and as
inexpensive as possible."
The thin film vaccine system was among the
undergraduate projects introduced to the public this month
at the university's annual Biomedical Engineering Design
Day showcase.
The idea originated last year at Aridis
Pharmaceuticals, a San Jose, Calif., firm that possesses
vaccine stabilization technologies and a rotavirus vaccine
that is made stable at room temperatures. Seeking a product
resembling breath-freshening strips to deliver the vaccine,
Vu Truong, co-founder and chief scientific officer at
Aridis, contacted Mao. Truong earned a doctorate in
pharmacology and molecular science from the Johns Hopkins
School of Medicine and knew of Mao's expertise in
biomaterials. Mao, an assistant professor of materials
science and engineering in the university's Whiting School
of Engineering, described the vaccine challenge to one of
his undergraduate lab assistants, senior Christopher Yu,
who became co-leader of the team that tackled the
project.
Initially, the students confronted several obstacles.
They were unable to copy the manufacturing process used to
make breath strips because its harsh solvent and high
temperatures would destroy the vaccine. They also needed to
devise a protective coating that would remain intact when
exposed to stomach acid but would dissolve in the
chemically neutral environment of the small intestine.
Through extensive research and testing, the students
solved these problems. They refined a room-temperature
production and drying process to make the strips and
identified an FDA-approved biocompatible polymer coating
that would protect the vaccine from stomach acid but
release the medicine in the small intestine. The coating is
pH-responsive, meaning it delivers its medical payload only
when the acid-alkaline level in its environment is
appropriate.
"What the students have accomplished is a way to
incorporate a pH-responsive polymer system that works with
an oral quick-dissolving thin film," Truong of Aridis said.
"It's still very early in the process, but the pieces
they've come up with have been very encouraging. We have
the delivery vehicle prototype. I'm optimistic that we can
make this work with our vaccine.
"I was pleasantly surprised," Truong added. "Professor
Mao entrusted this project to some cream-of-the-crop
students, [and] they have delivered the kind of results
that even seasoned professionals might not have
delivered."
Truong said his company is in talks to fund further
research in Mao's lab to refine the strips so that they can
dispense the Aridis rotavirus vaccine. Animal testing could
begin later this year, he said. "This is probably the
second-most-important childhood vaccine needed in the
developing world, right behind a malaria vaccine," he said.
"The mortality rate is high."
The student inventors said they are pleased about the
potential public health benefits of their work, and that
they found the hands-on assignment to be a valuable part of
their engineering education. "This was a really good
experience," said Yu, co-leader of the student team. "When
you run into problems in a project like this, you have to
think hard about how to solve them or work around them.
It's much more rewarding than a basic textbook problem,
where there's an expected answer and you don't necessarily
have to think as broadly or as creatively."
Yu, who is from Shreveport, La., and the other team
leader, Rohan Agrawal, of Tampa, Fla., have been accepted
into the biomedical engineering master's degree program at
Johns Hopkins. The other members of the team were Yang Li,
a senior from San Antonio; Dhanya Rangaraj, a junior from
Foothill Ranch, Calif.; Jonathan Yen, a freshman from
Hillsborough, Calif.; Shaoyi Zhang, a freshman from San
Jose, Calif.; and Judy Qiu, a freshman from Potomac Falls,
Va.
The project was funded by the Mao lab and by a $16,000
E-Team grant from the National Collegiate Inventors and
Innovators Association.
Robert H. Allen, an associate research professor in
the Department of Biomedical Engineering, was technical
adviser for this project and director of the design
course.
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