delivery: Beyond patches and pills
the industry has made significant advances in drug delivery, promising
technologies still lie ahead, says Meena Shah
less than 20 years, the field of drug delivery has gone from a fledgling
pharmaceutical art to a $20-billion global industry. And while these
years have seen impressive advances from nicotine patches
to nasal inhalers the most promising technologies still lie
ahead. This burgeoning area of research could someday produce an
insulin pill for diabetics, an under-skin pharmacy on a microchip,
and even lab-grown organs for transplants and plastic surgery.
the American Chemical Societys ProSpectives Conference, Future
directions of drug delivery technologies, in Boston in October,
scientists from around the world came together to discuss where
the field is going and what the biggest developments will be in
the coming years. The research that was presented focussed primarily
on two aspects of the field: traditional drug delivery and tissue
main goal of traditional drug delivery research is, quite simply,
to do away with needles. Nobody likes them, yet thousands of people
with diseases like diabetes and multiple sclerosis rely on injections
because their treatments are based on large protein molecules that
must be delivered intravenously to avoid getting devoured in the
stomach. This research looks for less invasive and more efficient
ways to deliver therapies, such as patches, inhalers, ultrasound
and, of course, pills, which still seem to be the overwhelming preference
than half of todays medical problems, however, cannot be treated
with drugs. Say somebody is dying of liver failure,
says Robert Langer, PhD, a professor of chemical and biomedical
engineering at Massachusetts Institute of Technology, theres
no drug to treat them; the only way to treat that person is if somebody
else dies, then you do a transplant.
approach this problem, Langer pioneered the field of tissue engineering
delivering cells to the body, not just drugs. Cells are inherently
intelligent; if you provide a polymer support system, they will
organize themselves on this scaffolding to create new tissue. The
scaffolding eventually degrades, leaving only the living cells.
In this way, scientists believe they can grow new cartilage, bone,
skin and eventually entire organs. Following are some of the
technologies that researchers expect to be available in the next
mice and men perhaps youve heard about the mouse with
the human ear a tissue engineering triumph where researchers
grew a human ear in the lab, attached it to the back of a mouse
and watched it thrive. Or how about the boy with a lab-grown chest?
He was born without any bones or cartilage on his left side, so
scientists grew him a new chest from his own cells. These experiments
were merely the first frontier for the field of tissue engineering,
and they hint at an incredible future.
scientists from Langers lab made a polymer scaffold that mimics
the spinal cord. They created paraplegic rats by placing
a defect in their spinal cord that hindered the use of their hind
legs. The researchers placed neuronal stem cells on the polymer
scaffolds and implanted them in the rats. After a while, the rats
with the implants could actually support their own weight.
isnt a total cure, Langer says, but its certainly a
step in the right direction toward helping those with paralysis
to someday walk again. The knot that ties itself sometimes
surgeons do operations in areas of the body that are very hard to
access, making it almost impossible to tie a suture. To help them,
scientists have manipulated tissue-engineering polymers to make
materials that change shape upon a change in conditions such
as the change from room temperature to body temperature.
technology may lead to a suture that can be tied loosely and then
placed in the body, where it automatically tightens itself. The
materials could also be used to make new blood vessels and cardiovascular
stints that can be placed through tiny incisions and then expand
to their proper shape.
can take a pill to treat headaches; why cant we take a pill
to treat diabetes? asks Nicholas Peppas, Ph D, formerly
of Purdue University, now with the University of Texas. The reason
is that insulin is a large protein molecule that gets digested in
the stomach. Researchers, however, are creating a pill that survives
the stomachs acids and carries insulin safely to the bloodstream.
At least 11 companies are working on developing such a pill right
now. Peppas is also developing a pill for the release of calcitonin
to treat osteoporosis.
on a chip
trouble remembering to take your medicine? Langer and others are
developing a microchip that can be implanted under the skin to deliver
drugs on cue. The chip has tiny reservoirs that can hold different
types of medicine as well as varying doses of the same medicine.
It can be programmed to release drugs at specific time intervals,
and it could also change the way we think about medical recording.
Every time you take a drug, it could actually transmit
from the chip to the computer
at your house, to the doctors office or hospital,
of simply treating diseases, drug delivery researchers hope to devise
ways to prevent them before they start. To this end, they are developing
nanoparticle sensors tiny particles on the order of a single
atom that will recognize compounds, such as glucose and cholesterol,
whose overproduction may signal disease. The particles will then
trigger a mechanism that tells a system (like the pharmacy on a
chip) to release another compound to deal with the chemical imbalance.
These nanoparticles are biodegradable, and they will self-destruct
after two or three days.
Star Trek, when the ships doctor, Bones, would
zap people with his painless gadget to give them their medicine?
Weve actually worked out a way to do that with
ultrasound, Langer says. Placing a small ultrasound
device against the skin for 15 seconds makes it more permeable,
allowing larger molecules to enter the bloodstream. The device could
be used to painlessly deliver large drugs like insulin or lidocain
a local anaesthetic that normally takes effect after about
an hour. With this system, lidocain can be put directly on the spot
where the pain occurs to provide relief within minutes. The ultrasound
makes the skin permeable in both directions, not just allowing large
molecules to enter, but also letting them out. Not only
could you deliver drugs non-invasively, but you could go the opposite
direction, Langer says. You zap yourself
for 15 seconds in the morning, put [a sensor] on, and every four
seconds you get a readout of what your blood-sugar level is.
ProSpectives is a series of small conferences for industry scientists
that examine a fields consequential topics through presentations
by its foremost researchers. Six conferences are scheduled for 2003,
including sessions on combinatorial chemistry and proteomics.