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The newspaper of The Johns Hopkins University May 29, 2007 | Vol. 36 No. 36
Quick-Dissolve Strips Could Curb Illness That Kills Kids BME undergraduates devise novel drug-delivery system to fight rotavirus

A team of seven biomedical engineering undergraduates has developed a quick-dissolving film that may someday deliver rotavirus vaccine to infants in impoverished areas. Co-leader Christopher Yu holds a sample of the material. Behind him are team member Dhanya Rangaraj, co-leader Rohan Agrawal and faculty adviser Hai-Quan Mao.
Photo by Will Kirk / HIPS

By Phil Sneiderman

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.


Related Web sites

Johns Hopkins Department of Biomedical Engineering
Hai-Quan Mao's Web page


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