Electricity Can Pump Medicine in Implanted Devices

Originally Published MDDI June 2002

R&D DIGEST

Engineers at Ohio State University (Columbus) have developed a computer model to help tiny medical implants dispense drugs on demand—electrically. The research may lead to more effective—and more convenient—forms of chemotherapy.

Nanotechnology shows a great deal of promise for delivering drugs inside the body. Yet researchers have had difficulty in developing systems capable of pumping fluids through the tiny passages within such devices, according to Terry Conlisk, professor of mechanical engineering at Ohio State.

Conlisk and his colleagues believe that a very small amount of electrical current may solve that problem. The engineers have developed the first comprehensive computer model to study the behavior of electrically driven fluids in channels.

Tests with actual nanometer-sized channels were conducted at iMEDD Inc., a commercial company cofounded by Mauro Ferrari, professor of mechanical engineering and director of Ohio State's Biomedical Engineering Center. The tests used technology patented by iMEDD and Ohio State. The model was proven effective in tests where electrical potentials as small as 1 V were able to drive saline through channels only a few nanometers wide.

"Pushing fluid through a very small channel requires a lot of pressure," Conlisk said. "Of course, you can't use pressures like that inside the body. So if we can drive fluid safely and effectively with electricity instead of pressure, that's a real advantage."

"The basic principle has been around for a long time. If a fluid is positively or negatively charged, and we apply a like charge to the inner surfaces of a channel, the charges will repel each other," he continued. "The fluid will flow down the channel." Hansford notes that while previous studies have focused on electrical techniques for transporting fluid, no other projects were as broad in scope. "Other research has involved either purely theoretical or purely experimental work, but our approach combines both, for channels in a wide range of sizes," says Hansford.

The computer model by the Ohio researchers yielded results that closely matched those from the experiments at iMEDD. In those experiments, engineers were able to flush nearly 0.5 nl of saline per minute through a channel only 7.0 nm wide. In a 20-nm channel, the flow rate was nearly 0.8 nl/min.

The computer models were based on electrical potentials as large as 6 V. The Ohio State studies, however, showed that much smaller voltage levels could be just as effective.

In practice, says Conlisk, the voltage needed would depend on the size of the implantable device and the amount of drug that had to be dispensed. He explains that these electrical charges would not be dangerous to patients because they are extremely small, and would not contact the body. The charges would flow only along the tiny channels inside the device, he says, adding that "you could run the device continually, and not even get a buildup of heat."

According to Tony Boiarski, PhD, who leads iMEDD's product development unit, "several existing drugs (e.g., interferon for treatment of hepatitis C or multiple sclerosis, and erythropoietin for treatment of low red blood cell count following cancer treatment) and many new ones are protein or peptide based." The high molecular weight of these biological drugs preclude their being taken orally. He adds that, because of their short half-life, "these molecules are quickly cleared from the body, so they must be administered by frequent subcutaneous injection (e.g., one to three times per week). Even with frequent injections, the level of biological drugs in the blood varies widely (because of the clearance issue). High levels are encountered after injection that can lead to unwanted side effects. Further, low levels (below the therapeutic value) can occur several days after injection, which can diminish the drug's effectiveness (and therefore diminish the ultimate outcome of the treatment)."

Boiarski also notes that injections are considered to be safe and reliable in a hospital setting. In some cases, however, patients are asked to self-administer biological drugs by subcutaneous injection over a course of certain therapies.

He explains that, in such situations, compliance problems can occur. "An implant would eliminate the need for frequent injections (which would improve compliance)," he says. Boiarski adds that the implant could also "deliver the drug at approximately constant levels, so better patient outcomes, and a more effective drug therapy, should result."

Certain low-molecular-weight drugs that can be taken orally could also be administered by an implant if patient compliance becomes an issue. For example, antipsychotic medications to treat schizophrenia or naltrexone to treat alcoholism or heroin addiction.

According to Boiarski, a controllable-dose implant (like the nanopump) would have several advantages. The first is that "dose rate could be modified or adjusted by the caregiver to optimize the treatment for a specific patient," Boiarski explains. He adds that, "dosing could be stopped if the patient was not tolerating the drug. In the case of pain medication, the patients themselves could regulate the dose up or down to accommodate their needs." He believes that the second advantage is that "dosing could be timed to daily, or monthly, schedules to mimic the body's own release scenarios (e.g., hormones)." "Finally," says Boiarski, "modulating the dose of a drug may also improve its therapeutic value by minimizing receptor down-regulation" that can result in desensitization.

Boiarski says the next hurdles to development include "design and development of a prototype nanopump implantable drug-delivery device and collection of long-term in vitro, and then in vivo, data." He estimates that it could be three years before in vivo testing of such a system begins.

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