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Revolutionizing drug delivery with a tiny syringe

By Melinda Levine

Malaria kills more than one million people yearly, according to the World Health Organization, and typhoid strikes 17 million each year. In parts of Southeast Asia and Africa, polio outbreaks still occur. Whooping cough hit Afghanistan earlier this year, and last year in sub-Saharan Africa alone, 3.5 million people were infected with HIV. Deadly diseases continue to ravage developing nations, where medical help or clean water can be hard to find. But a minuscule drug delivery system that is impervious to tropical heat, can be stored indefinitely, does not require a clean water supply, and can be painlessly self-administered may one day transform how these diseases are treated.

Liepmann image
Boris Stoeber (right) gently presses the MEMS chiclet on Dorian Liepmann’s hand, all it takes to deliver a life-saving dose of antibiotics. Stoeber fabricated the 10 mm x 10 mm MEMS syringe prototype in the Berkeley Microfabrication Lab, a project funded by the Defense Research Projects Agency, and Becton, Dickinson and Company.
PEG SKORPINSKI PHOTO

New technology emerging from Berkeley’s bioengineering labs could revolutionize the treatment of deadly diseases that threaten rural populations from the highlands of Kenya to the townships of Kentucky.

"By finding an alternative way to deliver drugs, we can open the door to more effective treatment of life-threatening illness," says Berkeley bioengineering professor Dorian Liepmann, who has been looking at new ways to deliver lifesaving drugs for almost a decade. Liepmann and post-doctoral researcher Boris Stoeber have developed a microelectro-mechanical system (MEMS) syringe — a fingernail-sized syringe, dubbed a chiclet for its resemblance to the squares of sugarcoated gum by the same name. The chiclet delivers a freeze-dried drug painlessly into the skin through an array of microneedles.

With oral medications, only about 10 percent of the actual dose reaches the blood system, says Liepmann. "But with the delivery system we are developing, nearly the entire dose hits the bloodstream immediately, making it infinitely more efficient," he says.

The chiclet seems simple in construct: a flexible shell made of silicone rubber, a drug suspension in a reservoir and, in a chiclet-sized syringe, up to 100 hollow silicon microneedles. Yet the device is anything but simple. It is designed to contain lyophilized, or freeze-dried, compounds that are extremely stable. To deliver the drug, the syringe is pressed against the skin for a few seconds. That pressure pushes the suspended dry drug out of the reservoir and into the microneedle channels, then out the microneedle tips and into the skin, where the body’s own interstitial fluids assist in rapidly absorbing the drug directly into the bloodstream.

The targeted site in the epidermis is out of reach of sensitive nerve endings so, unlike deep injections from stainless steel needle syringes, this device comes pain-free. "Imagine children getting their childhood vaccinations without shedding a single tear," says Liepmann.

Storage and safe delivery are the two main problems medical personnel confront in getting certain drugs into remote areas where there are no trained medical workers to mix up the drug compounds with sterile water or to administer an injection and no electricity to power coolers, Liepmann explains. Some drugs, like antibiotics routinely prescribed to children — from amoxicillin to penicillin — must be refrigerated after they’ve been reconstituted into liquid form. "MEMS syringes could be kept anywhere, even in a Quonset hut, and delivered by anyone," he says.

Stoeber image

This neon-lit, transparent microfluidic device, seen here on an inverted stage microscope, allows Stoeber to visualize the route particles travel as they enter a small channel, much like the microneedle channels in the chiclet-sized syringe.
PEG SKORPINSKI
PHOTO

Many drug compounds are unstable when mixed with aqueous liquids. But storing drugs as freeze-dried compounds, as the chiclet does, assures a long shelf life. These syringes can be shipped and stored at any temperature, require no preparation with water, and perhaps most crucial, the drugs they carry can be self-administered.

"The MEMS syringe will be attractive to developed countries too," adds Stoeber, whose work focuses on microfluid mechanics. "It could make drugs available that have been avoided because taking them orally causes liver and kidney damage. Drugs delivered through the MEMS syringe would bypass the liver, directly entering the bloodstream."

According to Liepmann, the chiclet will work best for those drugs that don’t require precise doses — drugs like antibiotics and vaccines that are not supersensitive to overdoses. This is because the amount of pressure a finger exerts on the flexible reservoir determines how much medicine is delivered, and this varies from dose to dose and person to person.

Even with the limitations of imprecise dosage confining the MEMS syringe to delivery of specific drugs, the field of opportunity for this syringe is enormous, says Stoeber. "It’s easy to use, inexpensive to produce, and doesn’t require trained personnel or sophisticated storage facilities," he says. "It really could improve health care in the Third World and beyond."

Although the project is still in its early stages, Stoeber has completed tests of the chiclet on chicken breast tissues, where a suspension of microparticles was successfully delivered at the target depth with good results. And preliminary clinical trials, where drug absorption by the body can be monitored, are set to begin this spring at University of California, San Francisco Medical Center.

Fussball image
Fussball in Liepmann’s Microfluids Research Lab is an all-time leveler and stress reducer. "We work collaboratively," says Liepmann, who holds the Lester John and Lynne Dewar Lloyd Distinguished Professorship in Bioengineering. "My students are colleagues. But," he says, "if they beat me at Fussball, I add chapters to their dissertations."
PEG SKORPINSKI PHOTO

"We need to see just how far the needles have to go in and how large they have to be," Liepmann says. "We’ve proved the principle. Now we have to move on to clinical trials with specific drugs — the final validation of the drug delivery concept."

Future applications for the MEMS syringe are numerous. Paramedics could shave off precious minutes in an emergency preparing a lifesaving syringe. NASA has always sought compact, light, ready-to-use drugs for astronauts aboard a spacecraft. And in the event of a bio-terrorist attack, the MEMS syringe would make it easier for large numbers of sickened people to receive quick treatment.

Two years ago a yellow fever epidemic in Guinea threatened the lives of several million people because 1.5 million doses of vaccine could not be delivered. "The chiclet could provide a way for the rapid deployment of medication, anywhere in the world," says Liepmann.


Melinda Levine is an Oakland-based book editor and freelance writer specializing in health, technology, and community relations.



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