Drug Patch Might Solve Woes With Oral Cancer Agent

Nick Mulcahy

September 09, 2011

September 9, 2011 — A promising agent for the prevention of oral cancers might eventually reach its potential, thanks to a novel drug delivery system, suggests a paper published online June 15 in Pharmaceutical Research.

A medicated oral patch, developed by researchers at the Ohio State University Comprehensive Cancer Center in Columbus, releases that agent — fenretinide — directly and continuously into precancerous lesions in the mouth.

The researchers conducted preclinical testing of the fenretinide patch, including in simulated saliva. In lab animals, therapeutic doses were achieved without detection of the drug in the system or surrounding healthy tissue, report the authors.

"These results are very encouraging. Fenretinide is a drug that scientists have studied as a cancer-preventing compound for decades, and with this mucoadhesive patch, we finally developed a way to harness its potential," said coauthor Susan Mallery, MD, in a press statement.

Fenretinide, which is a synthetic derivative of vitamin A, seems tailor-made for treating oral epithelial dysplasia, which is a precursor to oral squamous cell carcinoma, explain the authors.

Fenretinide "is a superlative inducer of epithelial differentiation (at lower doses) as well as apoptosis (at higher doses) in vitro," they write. "As a result of these positive in vitro attributes, numerous oral cancer clinical trials have evaluated fenretinide."

However, once in the body, fenretinide has been less than stellar.

"Complications such as low bioavailability and rapid drug elimination from the body, along with toxicity (e.g., mucositis and hyperlipidemia), originating respectively after oral and intravenous administration, have impeded its use in chemoprevention for oral and other cancers," they write.

Local drug delivery makes sense for fenretinide because it is "highly effective in providing therapeutic drug levels directly to the site of numerous cancers," say the authors.

Local drug delivery is also a good fit for the oral mucosa, the authors add. "Due to anatomic considerations, which include capacity for direct visualization (which enables monitoring of therapy and direct placement of drug delivery system), oral mucosa is more amenable to the use of local drug delivery strategies," they report.

The question became: Which local drug delivery system for the oral cavity was best for fenretinide?

There was no shortage of candidates. "Numerous kinds of devices, such as tablets, films, patches, disks, strips, ointments, and gels, have been studied for oral transmucosal drug delivery," write the authors.

But mucoadhesive patches offered the best mix of qualities. They are "highly flexible" and "better tolerated by patients than tablet formulations." Also, "patches are more efficient in providing accurate dosing and effective localized delivery of drugs" than gels and ointments, say the authors.

Dr. Mallery summarized the delivery system decision. "The challenge with oral gels and 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," she said

The patch consists of 3 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 that the medication stays within the patch.

The researchers plan to test the patch as a treatment for oral epithelial dysplasia in patients at their dental clinic. An estimated 300,000-plus people develop precancerous lesions in the mouth every year, according to the press statement. Annually, more than 36,000 people develop oral cancer and 7000 die, the authors report.

Pharm Res. Published online June 15, 2011. Abstract

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....