MIT researchers have developed a medical-device coating that releases precise doses of drugs under the control of electrical signals. The thin film, which consists of only the drug itself and an electrically active compound, might be coated onto stents, knee replacements, and even fully biodegradable patches of polymers for drug delivery. The researchers say that any therapeutic substance, from anticancer drugs to antibiotics, could be used in the coating.
The films, only a few hundred nanometers thick, are made up of layers of drugs and layers of a compound called Prussian blue. Prussian blue is commonly used as a dye. It has also been used to develop displays because it changes its color and charge when an electric field is applied. The films, developed by Paula Hammond, a professor of chemical engineering at MIT, take advantage of this change in charge, from negative to neutral. Hammond’s films are put down layer by layer: a layer of drug, which must be positively charged or encapsulated in a positively charged carrier, followed by a layer of Prussian blue. With the application of an electric field, the top layer of Prussian blue is switched to an electrically neutral state, the top of the film destabilizes, and a layer of drug is released.
Hammond says that the timing and level of the dosages released from the film can be very closely controlled, depending on how much drug is loaded into each layer and how many layers are allowed to disintegrate before the electric field is turned off. So far, Hammond has demonstrated a four-layer version of the film with a model drug. She believes that the films could be made up of many more layers and might be laid down on devices in patches, each of which might contain a different type of drug. Prussian blue has more than one charge state, so it’s possible to make films that are activated by different strengths of electrical fields; such films could release different drugs at different times.
If implanted close to the skin, the films could, in theory, be activated using an electric field applied from outside the body. Implants deeper in the body might need to be packaged with a battery and a sensor that could convert externally applied radio-frequency signals into electrical pulses to activate drug release.
Drug-releasing stents and other medical devices are typically passive, releasing compounds as the coating degrades inside the body. Hammond’s film provides a degree of control previously only possible using devices like insulin pumps or silicon-based chips with microfabricated wells full of drugs. (See “Delivering Drugs with MEMS.”) “Controlled release is a very new and unique property” of Hammond’s film, says Nicholas Kotov, associate professor of chemical engineering at the University of Michigan.
Because these films are potentially compatible with most medical devices, there are many possible uses. Kris Wood, a postdoc at the Broad Institute, in Cambridge, MA, who has worked with Hammond on the film, says that the first application they’re pursuing is cancer treatment. During surgery, doctors can’t always remove all traces of a tumor. When cancer tissues are left behind, the disease can recur. After a tumor has been removed, says Wood, doctors could line the tissue that bordered it with a biodegradable polymer coated with a thin film containing anticancer drugs. “You could then administer the drug in a highly localized way,” says Wood.
An important unanswered question, says Kotov, is whether or not there is a limit to how much drug can be loaded into Hammond’s films. Devices coated with the films could deliver relatively low doses of therapeutic compounds because their release would be highly localized. However, if such implants could provide only a limited number of doses and had to be replaced, this would increase the risk of complications. But because Hammond’s films are constructed layer by layer, Kotov says, “I suspect the maximum amount of drug that can be accumulated can be quite high.”
Hammond is currently making films that incorporate paclitaxel, a drug commonly used to treat breast and lung cancer. If she can demonstrate that such films are stable, Hammond hopes to then test them in animals.
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