Skin.The human body is covered in 21 square feet of the stuff. Skin weighs in at 7 to 8 pounds per person, and it's composed of around 300 million cells.
Scientists are targeting skin, the largest organ in the human body, in their drug-delivery research with new therapeutic drugs.
And drug-delivery expert Audra Stinchcomb at the University of Kentucky knows what she's up against: "The skin was designed to keep chemicals out of the body, so our challenge is to find exactly the right molecules with the right chemistry to penetrate the skin."
Audra Stinchcomb, an assistant professor in the UK College of Pharmacy, is developing a first-of-its-kind skin patch that can deliver anti-nausea marijuana-like chemicals to AIDS and cancer patients.
Transdermal (skin) patches, a technology born in the 1980s, are the delivery system of choice. Patches are composed of a drug dissolved or dispersed in a porous material. The patch is backed with paper, plastic or foil, plus adhesive. A special membrane controls the rate at which the drug inside the patch can pass through the skin and into the bloodstream.
Magazine and TV ads tout the convenience of patches for everything from motion sickness and pain relief to smoking cessation, birth control and hormone replacement. But Stinchcomb's targetscancer and AIDSare new to patch delivery.
Patches offer many pluses when you compare them to pills, and that's especially true when you're talking about cancer and AIDS.
"Patient compliance is so much better with patches," says Stinchcomb, who was recruited to UK in 2001 from the Albany College of Pharmacy as part of Kentucky's Research Challenge Trust Fund initiative. "Because patches can be worn for up to a week, patients don't have to worry about taking tablets multiple times a day.
"Also, we can put less of the drug in a patch for the drug to be effective because it bypasses the liver." She explains, "The liver chews up a lot of drug after you swallow a tablet or capsule. And patches are good because you get a nice steady delivery rate of drugs into the body, rather than peaks of drugs like you would with an immediate-release tablet. A steady trickle can decrease side effects."
But the big plus for patches, Stinchcomb says, is their ability to bypass the stomach. "Because the patch releases drugs directly into the bloodstream, they are less likely to cause stomach side effects like nausea." And that's important for people with AIDS and cancer, people whose very treatment regime makes it difficult to keep food down.
Building on the patch's anti-nausea benefit, Stinchcomb looks for chemicals "born" to cross the skin. "Only a few drugs naturally lend themselves to delivery through the skin," says Stinchcomb, who has been focusing on transdermal drug delivery since she entered grad school at the University of Michigan in 1989. "I look for drugs with penetrating properties that are already in other dosage forms. That's how I got into cannabinoids. They have a pretty good chemistry to go through the skin, and they're very potent."
She's working with synthetic cannabinoidsmarijuana-like chemicalsthat are created in the laboratory, not taken from the illegal plant. (Smoking marijuana for medical purposes is outlawed in most states.)
Cannabinoids are the only drugs that simultaneously increase appetite and decrease nausea and vomiting, and Stinchcomb says that's vital for AIDS and cancer patients. Marinol, a capsule using a synthetic form of THC (the main intoxicating chemical in marijuana), was approved by the FDA in 1985, but "if people can't keep the pill in their stomach, it can't do its job."
So Stinchcomb formulated a plan: create a first-of-its-kind prescription patch, a safe and legal method to deliver marijuana-like chemicals to ease nausea and stimulate appetite in people with AIDS and cancer.
And in 2000 her idea earned her $361,000 in research fundingthe first grant from the American Cancer Society to fund a marijuana-related research project. "Why did they buy into this? I think they wanted to show they were interested in cancer survivors, as well as treating the disease itself," Stinchcomb says. Pain and nausea are inevitable byproducts of the chemotherapy and radiation cancer patients face as they go through treatment.
About 60 of the 400 chemicals scientists have identified in marijuana are cannabinoids, and Stinchcomb evaluated a dozen of their synthetic counterparts for use in her patch.
Research with cannabinoids falls under the U.S. Drug Enforcement Administration's Schedule 1 controlled-substance category and requires a permit. "When I applied for my first DEA license at the Albany College of Pharmacy, before I came here, it took nine months just to get the permit to start the project," she says.
So why did she pursue cannabinoidswas she just a glutton for punishment?
Stinchcomb laughs and says the red tape does deter many scientists. "It's definitely part of the problem, because who wants to wait nine months to do a research project?" Things were significantly simpler when she came to UKthe university has a blanket license from the DEA that allows research on controlled substances once the project protocol is approved.
"We keep a very specific inventory of the synthetic chemicals we purchase, and everybody on the project has to get a DEA background check. But any hassles are outweighed by the enormous research potential," says Stinchcomb, who is seeking funding from the American Cancer Society and National Institutes of Health to continue this project. "A lot of people believe cannabinoids are the future of pain relief."
Easing the pain of multiple sclerosis and neuropathy (a common type of nerve damage) are just two of the possible applications of cannabinoid research. And unlike morphine-based drugs, cannabinoids wouldn't have side effects like nausea and dependency. The chemicals could also treat depression, Alzheimer's and Parkinson's disease.
Stinchcomb's cannabinoid studies, which began with lab experiments in 1999, led her to use a special specieshairless guinea pigsin early 2002. "This is the closest small animal model to human skin. We were excited to see that our cannabinoid patches were successful in getting therapeutic levels of drugs into the animals. That was a really big step for us," she says, noting, "We'll move on to pigs, next year. They're the best match to human skin."