The study evaluated the drug fenretinide, a synthetic derivative of vitamin A that has highly promising anti-cancer properties. Until now, scientists have failed to achieve a therapeutic, systemic dose of fenretinide because of drug toxicity and rapid release from the body. By using a new muco-adhesive patch invented by a team from Ohio State's Comprehensive Cancer Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) and the University of Michigan, the researchers developed a delivery system that can provide continuous drug therapy to saliva-coated oral tissue.
"The challenge with oral gels or rinses is the medication can dissolve in saliva before it penetrates into the tissue. This patch allows us to target and control drug delivery and tissue exposure," says Dr. Susan Mallery, an oral pathologist at Ohio State's Comprehensive Cancer Centre.
The patch consists of three layers: a disk saturated with fenretinide and polymers to make the drug more soluble in saliva, an adhesive ring to hold the disk in place, and a backing layer to ensure the medication stays within the patch.
In their study recently published online by the journal Pharmaceutical Research, Mallery and co-investigator, Dr. Peter Larsen of Ohio State, tested the fenretinide patch using simulated saliva as well as lab animals. In both situations, therapeutic doses comparable to levels needed in humans were achieved without detection of the drug elsewhere in the system or surrounding healthy tissue.
"These results are very encouraging. Fenretinide is a drug that scientists have studied as a cancer preventing compound for decades, and with this muco-adhesive patch, we finally developed a way to harness its potential," says Mallery.
It is estimated that more than 300 000 people develop precancerous lesions in the mouth every year. Nearly 36 000 people will develop oral cancer. Currently, there is no way to determine which of the precancerous lesions will turn into cancer. While dentists can opt to wait and observe the lesions, they often will surgically remove them for biopsies to determine the course of treatment.
"For people with several or recurring lesions, repeated biopsies can become painful and affect their speech, ability to eat and quality of life," says Larsen, who is chair of the division of oral and maxillofacial surgery and pathology at the Ohio State University College of Dentistry. "Ideally, we would like to have a way to slow down or even reverse the progression of these precancerous lesions without surgery. This medicated patch could be a solution."
Next, Mallery and her team of investigators will see if these lab results translate to humans, as they begin treating patients in their dental clinic with the fenretinide patch within about 16 months.
This research is supported by the Ohio State Centre for Clinical and Translational Science, a collaboration of scientists and clinicians from seven OSU Health Science Colleges, OSU Medical Centre and Nationwide Children's Hospital.
The Ohio State University Comprehensive Cancer Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centred care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centres and one of only seven centres funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 210-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top 20 cancer hospitals in the nation as ranked by US News & World Report.
