Working on a Medical Miracle

BY MARKETA SOUCKOVA

OSU team striving to create new drug delivery system

Ateam with OSU faculty members could end up revolutionizing the treatment of many diseases.

Joshua D. Ramsey, Ph.D., associate professor in the school of Chemical Engineering at OSU, is part of the team doing research for the Defense Threat Reduction Agency (DTRA) to develop a new drug delivery system.

“It is very exciting,” says Rob Whiteley, school head and Bartlett Chair of chemical engineering. “The fact that they are the first to achieve nanoparticle delivery internal to a blood cell is exciting and will have enormous impact on the field and on the School of Chemical Engineering.”

Ramsey is working with Carey Pope, Regents professor and Sitlington Chair in the Toxicology Center for Veterinary Health Sciences; Jing Pope, research associate professor of physiological sciences; Ashish Ranjan, assistant professor in physiological sciences; Steve Hartson, associate research scientist in biochemistry and molecular biology; and Stephen Brimijoin, professor and chair in pharmacology at the Mayo Clinic.

“It’s been a great project because of the expertise that all of the different people bring to the table,” says Ramsey.

Drugs that treat diseases or add protection from chemical warfare, tend to be cleared quickly from the body. OSU researchers recently designed a drugencapsulating nanoparticle capable of entering red blood cells.

“We started looking at ways to design a nanoparticle vehicle that could transport a bioscavenger protein to the body,” says Ramsey. “And can keep it there for around 100 days.”

Current efforts are focused on using this innovative delivery approach to protect soldiers and first responders from chemical weapons like sarin, a nerve agent that’s among the most toxic chemical warfare agents.

“This project has been a great opportunity for me to learn from excellent researchers across multiple disciplines,” says Nicholas Flynn, a doctoral student in chemical engineering. “I am excited to be part of a team that is working toward applying our research to solve a complex biomedical problem.”

“We are proud to join forces with OSU and its imaginative investigators for the good of our country, our military service members and our fellow citizens,” says Brimijoin.

The DTRA funded this research with a $3.3 million grant in August 2013, to cover the five OSU faculty members together with Brimijoin from the Mayo Clinic, and to cover all related expenses to the research.

The OSU team has recently begun testing on mice. The DTRA’s grant has provided funding for four years.

“My hopes are that, in the end, we will show something that works well in the animals and is very safe,” says Ramsey.

Experiments done on mice are executed in the Center for Veterinary Health Sciences, mostly done and led by Jing Pope and Ranjan. All animal-related procedures were approved and carried out under the guidelines of the OSU Animal Care and Use Committee.

Ramsey and his team in chemical engineering labs work with blood collected and provided by researchers from CVHS. They run in vitro tests to determine whether the nanoparticles attach to red blood cells and if they internalize within the cells.

“I am very excited about bringing my experience with material chemistry into this research project,” says Rangika Hikkaduwa Koralege, a post-doctoral student in chemical engineering. “And the great opportunity to learn more in-depth skills in biomedical research.”

Researchers are using a bioscavenger protein butyrylcholinesterase (BChE, a circulating protein that can bind to toxicants before they distribute to target issues) within a polymer (a large molecule composed of many repeated subunits) nanoparticle that is designed to target and internalize within red blood cells. The BChE protein is produced and supplied by Brimijoin and the Mayo Clinic.

Intravenous administration of BChE has been used in humans since the 1950s to treat organophosphorus intoxications and has been shown to be a stable, effective and safe bioscavenger against the most toxic organophosphorus-based nerve agents.

A drug-encapsulating nanoparticle system capable of entering red blood cells and extending the circulation time to approximately 100 days has great potential. In the future, treatment of blood-specific diseases, such as malaria, as well as many other diseases could be vastly improved.

The potential of this research is enormous and will have a great impact not only on chemical engineering and other OSU areas involved in this research, but on the United States as a whole.