Polymer Gel Holds Promise For Therapeutics Delivery And Tissue Engineering

Called a stimuli-sensitive polymer, the material is designed to change immediately from a liquid into a gel in response to stimulus, such as an increase in temperature. This feature would enable physicians to inject the mixture of the polymer and a medicinal solution directly into a specific target in the body, where it would warm and instantly gel.

"Stimuli-sensitive gels show promise for the effective treatment of inoperable tumors," said Anna Gutowska, senior research scientist at PNNL and lead developer of the gel. "While much more research remains to be done before this becomes an accepted medical procedure, we are very excited about its potential."

One of the more promising therapeutic applications is targeted delivery of medical isotopes or chemotherapy drugs to treat inoperable or difficult-to-treat solid tumors, such as those of the liver, pancreas, brain, breast and prostate.

This year, approximately 179,000 new cases of prostate cancer will be diagnosed, according to the American Cancer Society. The gel may be applicable as an improved therapy for early-stage prostate cancer, for example.

In this application, the polymer solution would be mixed with a medical isotope or chemotherapy drug, then injected into the tumor where body heat would cause instant gelling. Because the gel holds the therapeutic at the target site, developers anticipate being able to safely deliver a uniform dose to cancer cells while minimizing damage to surrounding healthy tissue.

In preliminary tests, the gel appears to hold therapeutic isotopes in place. Furthermore, the gel appears to be compatible with both beta- and gamma-emitting isotopes, which would enable physicians to select the most effective medical isotope for individual treatment needs.

While initial research was funded by DOE, PNNL now is applying National Institutes of Health funding to optimize the material's performance and investigate potential long-term toxic effects of leaving the material in the body, though preliminary studies show the gel to be benign.

In related research, PNNL is collaborating with the Medical University of South Carolina to test a biodegradable version of the polymer gel to support repair of articular cartilage - the durable type of cartilage that provides cushion between joints.

Once injured, articular cartilage doesn't heal well, or typically at all on its own. Consequently, more than one million cartilage repair surgeries are conducted annually. However, there are limitations to the effectiveness of these surgeries because physicians have been unable to spur growth of articular cartilage inside the body. Therefore, cartilage cells, called chondrocytes, instead are extracted from a different site within the body for cultivation in the laboratory. Not only does this create another defect, but physicians have been unable to cultivate chondrocytes with all the properties required to generate articular cartilage. Rather, a weaker, less durable type called fibrocartilage forms.

Through a two-year, DOE-funded project, Gutowska and collaborators at the Medical University of South Carolina are developing two components to support the successful repair of articular cartilage. The first is a three-dimensional cell culture system to support the in-laboratory growth of chondrocytes that retain the properties necessary for articular cartilage repair. A patent recently was issued for this technology. The second component is a biodegradable polymer gel that can be injected into the defect to serve as a temporary synthetic "scaffold" to support growth of the injected chondrocytes. Testing of the biodegradable gel currently is taking place at the Medical University of South Carolina.

"Our aim is to develop a gel that supports the propagation of articular cartilage-forming cells not only in the laboratory, but directly at the site of injury," Gutowska said. In addition, the three-dimensional cell culture system may be applicable to support future tissue engineering processes, such as the cultivation of stem cells from non-embryonic sources.

Business inquiries on polymer gel should be directed to Erik Stenehjem at 509-372-4212. Information on other PNNL technologies should be directed to 1-888-375-PNNL or e-mail: inquiry@pnl.gov

Pacific Northwest National Laboratory is a DOE research facility and delivers breakthrough science and technology in the areas of environment, energy, health, fundamental sciences and national security. Battelle, based in Columbus, Ohio, has operated PNNL for DOE since 1965.