In a recent article outlining the goals of the soon-to-be launched National Center for Advancing Translational Science (NCATS), NIH Director Francis Collins, M.D. noted that the current research process for discovering new therapies is often slow, expensive and unsuccessful. He went on to describe several ways that translational medicine could revolutionize the system, including the idea of “repurposing and rescuing drugs that could potentially have other uses” an idea being put into action at Ohio State with some help from That State Up North.
Ohio State University oral pathologist Susan Mallery and co-investigator Peter Larsen have teamed up with two University of Michigan pharmaceutical chemists to make fenretinide an oral cancer fighter.
For more than two decades, researchers have studied fenretinide, a synthetic vitamin A derivative. Its capacity to induce both terminal differentiation and cell death yielded highly promising results with cultured human cancer cells. Likewise, studies in lung, breast skin, prostate and bladder animal cancer models re-enforced fenretinide’s cancer-preventing effects at the in vivo level. However, when it came to prevention of oral cancer, which kills more than 7,000 people each year, fenretinide didn’t meet expectations. After multiple studies with lackluster results, oral cancer researchers moved away from fentretinide to look elsewhere for an answer.
“Istarted thinking maybe fenretinide wasn’t working as well because systemic administration can reduce compound activity, and the need for fenretinide to get from the underlying vessels to the target epithelial cells. It seemed unlikely that a therapeutic amount was actually reaching the lesions,” says Dr. Mallery, a professor of Oral Pathology at The Ohio State University College of Dentistry. “We needed to come up with a way to circumvent issues with poor systemic uptake by delivering the compound directly to the lesion. But, how do you deliver a water insoluble compound into a saliva filled mouth?”
So Mallery recruited the help of University of Michigan’s Steven Schwendeman and Kashappa Goud Desai to develop a first of its kind patch that sticks to the inside of the mouth, and delivers a continuous therapeutic dose of fenretinide directly to the precancerous lesion. The patch consists of three layers: a disk saturated with fenretinide and polymers that make the lipid soluble fenretinide better adsorbed in a water-rich environment, a secondary adhesive ring to hold the disk in place, and a final backing layer that ensures the medication stays inside the area of the patch. Patch formulation and in vitro and in vivo release kinetics were recently described in an article appearing in the journal Pharmaceutical Research (June 2011).