

For decades, this sponge-like quality has inspired the creation of cosmetic creams and pain-relieving sprays, and in recent years, the development of nicotine and hormone patches. But fewer than a dozen drugs can be delivered through the skin because it can effectively absorb only a handful of compounds under ordinary conditions.

Now, researchers are developing techniques to move a wider range of drugs across the skin barrier. Some work by making the skin more permeable, either by widening its pores through ultrasound waves or by softly puncturing the skin with a grid of microscopic needles. Other techniques use a mild electric current to propel the drug through the skin or tag drug molecules with compounds that help it slip in through pores.

Drug delivery with these techniques offers several advantages over pills and injections. It can ensure the steady release of medication into the patient's bloodstream over long periods, improving the efficacy of a dose. It can prevent the rapid breakdown that many drugs taken orally undergo when they pass through the digestive system.

Transdermal drug delivery is also painless and convenient -- a big advantage for patients who hate injections or forget to take their pills on time.

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''Consider the estradiol patch, which delivers a form of estrogen and is used in hormone replacement therapy,'' said Dr. Samir Mitragotri, a researcher at the University of California at Santa Barbara. ''You can put a single patch on the skin and get the drug for seven days. It's difficult to achieve the same effect with a pill or an injection.''

Unlike nicotine and oestradiol molecules, which can pass through the skin easily, the molecules of drugs like insulin are too large to pass. To deliver such compounds transdermally, Dr. Mitragotri and his colleagues are developing an ultrasound device that can enlarge pores by striking them with shock waves. A vibrating metal rod in the device sends sound energy rippling through a column of liquid to generate the shock waves.

A patient could strap the battery-operated device around an arm and switch it on for a few seconds. The skin in the area becomes highly permeable for 12 hours or so. A patch placed on the arm in this period could deliver medication that the patient's skin would ordinarily be unable to absorb.

''The device itself you could leave in the closet, and the patch you could wear to work,'' Dr. Mitragotri said. Sontra, a Cambridge, Mass., company founded by Dr. Mitragotri and his research partners, plans to sell the device as a system for delivering drugs like insulin and erythropoietin, which is prescribed for anemia. The two are now administered by injection. The company acknowledges that a commercial product is still a long way off.

Some transdermal systems are close to the pharmacist's shelf or already there. Most are based on a technology called iontophoresis, which involves using a low electric current to propel drugs through the skin. Since the drug molecules themselves bear a small charge, the current drives them across the skin barrier.

One system is being developed by Vyteris, a company in New Jersey. Designed to deliver lidocaine, an anesthetic, the system is a small wearable device containing a patch filled with the drug. The patch is connected to an electronic controller that can be programmed to deliver a desired level of current. Vyteris says the system has gone through trials and could be on the market by the end of next year.

''The nice thing about the technology is that you can increase or decrease the flow of the drug by ramping up the current or turning it down,'' said James Garrison, who oversees business development at Vyteris.

A wearable device developed by Cygnus in Redwood City, Calif., uses iontophoresis to monitor glucose level in diabetes patients. It actually performs the reverse of drug delivery, using a current to draw glucose through the skin. A sensor measures the glucose level, which shows up on an electronic display. GlucoWatch, as the device is called, can be worn around the wrist and provides a fresh reading every 20 minutes.

If more systems come to market, said Dr. Richard Guy, a pharmaceutical scientist at the University of Geneva and an adviser to Vyteris, transdermal delivery could become feasible for a wide variety of drugs. But most transdermal technologies, Dr. Guy said, are still far from ready.

''Technologies like ultrasound can open up the skin quite effectively for drug delivery,'' he said, ''but reducing them to a form that is practical and economic is not a done deal.''

Dr. Mark R. Prausnitz, a researcher at Georgia Tech, said the development of new drugs, especially proteins that cannot be administered orally, would help the transdermal market expand significantly. He said he hoped one product in that market would be what his group was developing at Georgia Tech: a microneedle patch for delivering vaccines, DNA drugs and other large, unwieldy molecules.

Dr. Prausnitz and his colleagues have designed arrays of microneedles, a ''microscopic bed of nails'' that can painlessly pierce the skin. The needles serve as channels for a drug to diffuse into the patient's bloodstream.

''A complete microneedle device could be the size of a Band-Aid, cost well under a dollar, require no batteries and cause no pain,'' Dr. Prausnitz said.

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