April 20, 2015
The UNC Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill has received $1.8 million through the Research Opportunities Initiative Awards from the University of North Carolina General Administration to support research into drug-delivery systems for treating cancer and other diseases.
The award funds two pharmacoengineering initiatives that bring together scientists at UNC and North Carolina State University. Pharmacoengineering is a discipline developed at the School that combines engineering and the pharmaceutical sciences to improve the delivery of medicines in the body.
The grant funds collaborations dedicated to addressing two research challenges:
- Treating brain cancer with genetically engineered stem cells
- Understanding the immune system’s response to man-made materials used in medicine
“These ROI awards will allow us to jumpstart research in a two very novel and promising areas of investigation,” says Michael Jay, PhD, the principal investigator on the grant and a Fred Eshelman Distinguished professor at the School. “This greatly speeds up our ability to build the body of work needed justify further support.”
Battling Brain Cancer
Shawn Hingtgen, PhD, converts ordinary skin cells to neural stem cells, loads them with medicine, and sends them in to fight brain cancer.
“Stem cells will home to cancer like they’re following a trail of breadcrumbs. It’s a really powerful delivery system for us,” says Hingtgen, an assistant professor at the School. “We’re able to engineer those cells to pump out anticancer drugs and deliver them to both the primary tumor and the invasive, distant tumor foci that are so hard to eradicate with traditional surgery, radiation, and chemotherapy.”
Surgery is usually the first step in treating most benign and many malignant tumors, according to the American Brain Tumor Association. Often tumors cannot be completely removed and tend to grow back. Hingtgen believes drug-packed stem cells placed in the cavity created by the removal of a tumor would mop up any cancerous cells that may have been missed or start to regrow.
However, he discovered that the stem cells tended to disappear before having the chance to do their work.
“In all the standard models, our stem-cell therapies worked so well,” Hingtgen says. “When we did it in the surgery models, everything failed. The cells disappeared very quickly; not enough of them remained to stop the tumor from growing back. We turned to pharmacoengineering to try to solve this unexpected challenge.”
What Hingtgen needed was a way to get the stem cells to hang around longer. He turned to Elizabeth Loboa, PhD, a professor at North Carolina State University who produces a textile made of extremely fine hollow fibers spun into a porous sheet. One use of Loboa’s fabric is as a smart bandage embedded with compounds that fight infection, regenerate tissue, and relieve pain. The material is very similar to the collagen matrix that gives structure to many of the body’s tissues.
“Dr. Loboa’s sheets are ideal to pair with our technology,” Hingtgen says. “We can grow the cells on these mats and then line the walls of the surgical cavity with them.”
Preliminary tests showed they could slow the growth of tumors by two to five times while doubling the overall survival rate in mouse models.
“We were able to greatly increase the number of cells available and prolong the amount of time the cells stayed in the area,” Hingtgen says. “By getting more cells in for a longer time, we really felt like we could improve the success of our tumor-killing therapy.”
The Research Opportunities Initiative Award allow Hingtgen to develop the ideal stem cell for his application and then work with Laboa to fine tune the scaffolding. This should allow the team create and test a product that is very close to a product that could be used to treat people, he says.
Sometimes the body can’t tell friend from foe, and people develop antibodies to more than viruses and bacteria. Assistant Professor Sam Lai, PhD, is concerned about the immune system’s response to materials used in medical products. Polyethylene glycol, or PEG, is one such material that is used in a number of medical applications, including nanoparticle drug-delivery systems.
“When you put synthetic materials into a person over a long period of time, the body might say, ‘Ah, this is something that is not part of me’ and start making antibodies against it,” Lai says. “That’s precisely what has happened to polyethylene glycol, a widely used polymer in the pharmaceutics industry.”
PEG is often used to improve the stability of medicine both in storage and in the body where it allows medicines to circulate longer. If a patient has antibodies that bind to PEG, medicines that are made with the polymer could be cleared out prematurely or otherwise affected by the immune system.
“This is an emerging issue as we put more nanomaterials into our bodies for therapeutic and diagnostic purposes or even for regenerative medicine,” Lai say. “We have very little information about how our bodies interact with these nanomaterials over long periods of time.”
The ROI award will allow scientists at UNC and NCSU to begin investigating how antibodies can evolve to recognize nanomaterials. The goal, Lai says, is to learn to compensate for the immune-system response and possibly develop stealthier materials that attract less notice in the body.
Lai is working with NCSU’s Loboa and with Zhen Gu, PhD, and Alexander Kabanov, PhD, DrSci, at UNC to test how certain polymers used in nanomedicines trigger the immunes system to create antibodies.
The team also includes Reuben Carbonell, PhD, Frank Hawkins Kenan Distinguished Professor of Chemical Engineering at NCSU; Michael Miley, PhD, director of the UNC School of Medicine’s Antibody Core Facility; and Greg Forest, PhD, the Grant Dahlstrom Distinguished Professor in the UNC Department of Mathematics.