Smart Drugs Get Zapped

For patients suffering from diseases such as cancer, treatment often requires taking pills on a complex schedule or receiving repeated injections. New, precise drug delivery systems would spare patients these hassles, while preventing side effects by targeting the drugs where the body needs them most. Now researchers report an injectable gel that releases drugs when stimulated by a weak electric field applied from outside the body (ACS Nano, DOI: 10.1021/nn203430m).

Several controlled drug release systems already exist, but they have significant drawbacks that may make them impractical for wide use, says Jun Ge, a postdoctoral researcher in the lab of Stanford University chemistry professor Richard Zare. Some researchers have designed electronic chips that store and release drugs. But implanting the chips—and, inevitably, taking them back out—requires surgery. Other researchers have turned to so-called smart materials that deliver drugs when triggered by laser pulses, ultrasound, or magnetic fields. But generating these signals requires complex instrumentation.

Zare’s group aimed for simplicity. They load drugs into smart materials based on conductive-polymer nanoparticles. When they apply a weak electric field, the charge of the polymer nanoparticles changes and they release their drugs. In the clinic, a doctor could create such a field using an AA battery. Zare and his team suspend these nanoparticles in a temperature-sensitive gel. It’s liquid at room temperature, so the researchers can inject the nanoparticles into tissues, but it turns into a gel at body temperature to hold the drug-loaded nanoparticles in place.

The Stanford group first tested their drug-delivery system by placing the gel-embedded nanoparticles in a buffer solution and monitoring how much of the chemotherapy drug daunorubicin or fluorescent dye fluorescein flowed out of the gel. They showed that they could control the dosage and timing of the drug release by varying the strength and duration of an external electrical field. For example, they found that when they applied an electrical field of -4.5 V per cm for 10 seconds every five minutes, each pulse released 20 ng of fluorescein from the gel. When the researchers increased the field strength to -13.6 V per cm, the gel released 60 ng per pulse.

They next injected nanoparticles loaded with a fluorescent dye under the skin of mice and watched the dye spread through the animals’ sides after they applied an electrical field. Ge says that these mouse studies also showed that the gel will break down completely after one to two months inside the body, with no apparent effects on the health of the mice.

Robert Langer, a biomedical engineer at the Massachusetts Institute of Technology, praises Zare’s work: “This is a very simple system” for drug delivery, he says, but it provides levels of control similar to those of more complex setups. He says the researchers next have to demonstrate they can control the dosage of drugs in animal tests. Indeed, the Stanford group is now doing such tests with support from the drug company Sanofi.