Beyond Patches And Pills: The Remarkable Future Of Drug Delivery

[Guest guest]

Source: American Chemical Society

Date:

11/26/2002

Beyond Patches And Pills: The Remarkable Future Of Drug Delivery

In 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.

At the American Chemical Society's 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 focused primarily on two aspects of the

field: traditional drug delivery and tissue engineering.

The 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 of patients.

More than half of today's medical problems, however, cannot be treated with

drugs. " Say somebody is dying of liver failure, " says Langer, Ph.D.,

a professor of chemical and biomedical engineering at Massachusetts

Institute of Technology. " There's no drug to treat them; the only way to

treat that person is if somebody else dies, then you do a transplant. " To

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 10-20 years:

Of mice and men -- Perhaps you've 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. Recently, scientists

from Langer's 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.

It isn't a total cure, Langer says, but it's 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. This

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.

An insulin pill -- " We can take a pill to treat headaches; why can't we take

a pill to treat diabetes? " asks 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 stomach's 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.

Pharmacy on a chip -- Having 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 that information from the chip to

the computer at your house, to the doctor's office or hospital, " Langer

says.

Self-destructing sensors -- Instead 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.

Ultra-easy ultrasound -- Remember " Star Trek, " when the ship's doctor,

Bones, would zap people with his painless gadget to give them their

medicine? " We've 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 anesthetic 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. "

ACS ProSpectives is a series of small conferences for industry scientists

that examine a field's consequential topics through presentations by its

foremost researchers. Six conferences are scheduled for 2003, including

sessions on combinatorial chemistry and proteomics. Further Information on

the Conference schedule is available at http://www. acsprospectives.org