Pills and needles, the traditional devices for delivering drugs into the body, are becoming Victrolas in a world of floppy disks. Young biotechnology firms and established drug companies from Cambridge, Mass., to Palo Alto, Calif., are developing new ways of sending just the right amount to just the right spot in the body at exactly the right time.
Although needles and pills are not likely to disappear, a number of technologies -- including Band-Aid-like patchs that slowly release drugs through the skin, implantable drug pumps that can deliver insulin to diabetics and chemotherapy to cancer patients, tiny pill-sized pumps that can be swallowed, drugs wrapped in fatty balls called liposomes and molecular homing devices called monoclonal antibodies -- threaten to replace them in some cases.
These new methods require smaller drug doses, reducing side effects. And a high-tech system can mean taking a drug once weekly instead of twice a day. Best of all, the drugs may work better because they are delivered more accurately.
Stomach acid wreaks havoc with many drugs taken as a tablet or capsule. The liver inactivates others before they have a chance to work. To compensate, doctors prescribe larger, more frequent doses.
Large doses create an unwanted "roller coaster" effect. When a person swallows a drug or receives a shot, the body is inundated with medication -- far more than would be necessary if so much weren't lost along the way. It's like flooding the entire Metro rail system to douse a trash can fire at Dupont Circle.
The new delivery systems can overcome these problems, but there are bugs to be worked out. The technology can't yet accommodate all drugs, and the new products will cost more. Development, however, is advancing rapidly.
Band-Aid style patches that slowly release drugs through the skin are already being used to deliver medicines to control motion sickness and angina pain.
The next drug to use the skin patch will be clonidine, for high blood pressure, which won government approval in this form late last year. The United States is the first nation to approve a through-the-skin blood pressure drug, and the move could launch a revolution in treating hypertension. The drug isn't new, but in tablet form it must be taken twice daily, while a single patch can control blood pressure for a week.
LecTec Corp. of Minnetonka, Minn., is working on an active transdermal system using a method called iontophoresis. This technology allows drugs with molecules normally too big to travel through the skin to be coaxed through with an electrical field.
That would open the transdermal drug delivery route to insulin, for example, for diabetics. Scientists envision a Dick Tracy wristwatch-style device that would create a weak electrical field and hold the drug against the skin. Years of development remain before it will reach the market.
Another Minnesota firm, Medtronic Inc., has developed a computerized, implantable drug pump called DAD, or drug administration device. It is now in clinical tests using anticancer drugs, pain killers and insulin.
This titanium hockey puck includes a microprocessor powered by a lithium battery. A doctor uses radio signals to instruct the device how much drug to dispense. The program can be changed any time, and DAD beeps when its drug reservoir runs low.
The drug is pumped to the desired place in the body through a tiny tube, and refills (by needle through the skin) are needed about every three weeks.
In future applications, according to Medtronic, DAD may be joined to a sensor that monitors a diabetic's blood glucose levels. The device could then act like an artificial pancreas, releasing insulin in response to changes in blood glucose levels.
Medications normally swallowed are also going high tech. Some products recently introduced use special "ionized" liquids. Another device looks like a pill but is actually a tiny pumping station.
The pump is an invention of Alza Corp. of Palo Alto, which calls the system OROS, for "oral osmotic." This two-stage device has a core of active drug and a semipermeable shell with a laser-drilled hole. As body fluids seep through the shell, the pressure of osmosis pushes the drug out the hole at a steady rate for up to 16 hours.
Similar technology has been developed by Pennwalt Corp., a leader in high-tech liquids, which developed the "Pennkinetic ion-exchanging resin system," the first technology for long-term controlled release of liquids.
Pennwalt takes a negatively charged ion and "loads" it with a positively charged drug. Since the charges are opposite, they stick, like magnets. That combo is then sealed with a coating. The thickness of the coating determines how fast the drug is released.
When negative ions naturally present in the body come in contact with the positively charged new arrivals, they exchange with the other negatively charged ions, and carry off the drug.
Nonprescription cough and cold medications that use this technology include Extend 12 and Cold Factor 12.
Though still experimental, two substances that have gained the drug delivery spotlight are liposomes and monoclonal antibodies.
Liposomes are tiny balloons made from artificial fat. Scientists discovered how to make these devices in the 1960s but only recently developed liposomes that don't spoil rapidly on the shelf.
The liposome surrounds the drug and keeps body fluids from dissolving it before it reaches its destination.
Once in the body, all fats -- including liposomes -- gravitate toward the organs responsible for clearing them out. The spleen, liver and lungs are examples, and early research has focused on using liposomes to deliver drugs against liver and lung cancers.
Some researchers believe that liposomes designed with a fat content matching that of other organs will be more likely to seek out those regions of the body.
The latest studies show that liposomes might be able to carry and localize drugs that otherwise would be dangerous to healthy cells.
For example, the powerful anticancer medication doxorubicin can severely damage the heart. But when hidden inside the belly of the liposome, the drug can safely pass through the heart, which plays no role in clearing fat from the body, and go directly to the liver, where it is released to attack the cancer.
Genetic engineering has produced perhaps the most exciting new development, monoclonal antibodies. The body naturally produces millions of antibodies that defend against all manner of invading bodies. With genetic engineering technology, scientists can manufacture artificial antibodies programmed to attack specific diseases.
These are known as monoclonal antibodies, and they can attack disease two ways. The antibody itself can drive out invaders, or a drug can ride along piggy-back style to provide reinforcement.
For example, monoclonal antibodies programmed to seek out specific types of cancer might also carry with them a drug effective against that form of cancer.
Antibodies attached to the highly toxic drug ricin are already helping patients undergoing bone marrow transplants. Ricin -- a protein so toxic that a single molecule can kill a cell -- is used to kill the harmful T-cells, a type of white blood cell that helps reject transplanted tissue. The poison rides aboard T-cell-targeted antibodies, and is used before the marrow is transplanted.
Such drugs are attached to monoclonal antibodies by creating a chemical reaction that causes them to stick together. The key hurdle is to spark that union without inactivating the drug, and it is a hurdle researchers can't yet consistently clear.
Both liposomes and monoclonal antibodies would most likely be given intravenously. They may be the closest things yet to the long-sought magic bullet against cancer and other dread diseases.