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