December 1, 2000

Commentary by Roger Martin Martin writes about research at KU for Kansas media and in a webzine. Contact Martin at rmartin@kucr.ku.edu or (785) 864-7239. Martin also can be heard on KANU 91.5 FM public radio Archives More articles by Roger Martin Subscribe now to receive KU News by email

Drug delivery research may help ease fear of doctors

by Roger Martin

The Dublin physician who invented the hypodermic syringe 156 years ago found one medicine particularly useful when injection was called for.

"The fluid I have found most beneficial," wrote Francis Rynd, "is a solution of [morphine] in creosote."

Perhaps Rynd's choice of fluids made his patients less reluctant to take their shots. But most of us, and especially kids, fear and loathe injection. So drug makers search for other ways to slip drugs into the body.

The first skin patch came to market about 20 years ago. It's used to treat motion sickness. Today, skin-penetrating drugs help treat heart pains, hypertension, menopause symptoms and nicotine cravings.

Yet fewer than two dozen drugs in all are delivered into the bloodstream through the skin.

Why? Because skin is one tough cookie.

About a tenth of an inch thick, it's composed of eight layers. The outermost, known as the stratum corneum, should have "keep out" signs plastered all over it.

The cells in the stratum corneum are thicker than those in the other seven layers. And the chemical mortar between them is tighter.

Only drugs built from small molecules have much luck passing through this layer of skin, says Howard Rytting, a University of Kansas pharmaceutical chemist who develops compounds that help drugs penetrate skin.

Trying to get some of the new genetically engineered molecules through the stratum corneum would be like squeezing a volleyball through a pinhole, he says.

Rytting has had some success though. A few years ago, he reported that harnessing one of his compounds to molecules of an arthritis drug made the drug 430 times more penetrating.

Recently, Rytting's research group has made a compound that enhances by a thousandfold the skin-penetrating power of prostaglandin E.

A company called NexMed is working to bring the product, in a cream form, to market.

Men who now use various forms of prostaglandin E to produce and maintain erections will sigh with relief if NexMed succeeds. The drugs are currently administered to the place they're needed with Dr. Rynd's fiendish tool.

Rytting says his compounds work by making the fatty walls of cells easier for drugs to penetrate. He tests his compounds' penetrating power by using the shed skins of black rat snakes.

Snakeskin lacks hair follicles but is otherwise much like our own stratum corneum.

Rytting thinks that in the future other nontraditional means of drug delivery will emerge, including inhalation of an increasing number of medicines.

As a boy, I remember getting shots for tetanus, smallpox, polio, measles, mumps, flu.

Worst of all were the rumors about the 21 painful shots I'd have to take -- in the stomach no less -- if a dog with rabies ever bit me.

And so, for the sake of all the boys and girls who dread needles and, therefore, visits to doctors and dentists, I wish Rytting and his colleagues good luck.