Thursday, February 28, 2008

Smart Coating Delivers Drugs

Electrical pulses control the release of drugs from a biodegradable thin film.

By Katherine Bourzac

Smart coating: Broad Institute postdoc Kris Wood, MIT chemical-engineering professor Paula Hammond, and MIT graduate student Daniel Schmidt developed a thin film for coating medical devices. The film (bottom), which contains vividly colored Prussian blue, releases drugs when an electrical field is applied. Credit: MIT News Office; Daniel Schmidt

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.