Nanoscale Thin Film Polymer Drug Delivery for Diabetes, Cancer

Researchers at MIT have developed a new thin-film coating that delivers precisely controlled drug doses to specific targets in the body following implantation, effectively becoming a sort of “micro pharmacy.”

The film could ultimately be used in the delivery of drugs for diabetes, epilepsy, cancer, and other diseases. It is one of the first drug-delivery coatings that can be remotely activated by applying a small electric field. The film, which is typically about 150 nanometers, or 150 billionths of a meter thick, can be implanted in the body.

“You can mete out what is needed, exactly when it’s needed, in a systematic fashion,” said Paula Hammond, chemical engineering professor of and senior author of a paper on the work[1] which appeared in the Feb. 11 issue of the journal Proceedings of the National Academy of Sciences.

Made from alternating layers of two materials, the film contains a negatively charged pigment and a positively charged drug molecule, or a neutral drug wrapped in a positively charged molecule.

The negative pigment, made from a nontoxic, FDA-approved, electroactive material known as Prussian Blue, sandwiches the drug molecules and holds them in place.

When an electrical potential is applied to the film, the Prussian Blue loses its negative charge, in turn causing the film to disintegrate, releasing the drugs. The amount of drug delivered and the timing of the dose can be precisely controlled by turning the voltage on and off.

As well, the electrical signal can be remotely administered, for example, by a nurse, using radio signals or other techniques that have already been developed for other biomedical devices.

Chemotherapy and other Applications

The films can carry discrete packets of drugs that can be released separately, which could be especially beneficial for chemotherapy. The research team is now working on loading the films with different cancer drugs.

In the future, devices could be designed which would automatically deliver drugs after sensing that they’re needed. For example, they could release chemotherapy agents if a tumor starts to regrow, or deliver insulin if a diabetic patient has high blood sugar.

“You could eventually have a signaling system with biosensors coupled with the drug delivery component,” said Daniel Schmidt, one of the papers lead authors.

Because these films are built layer by layer, it is easy to manipulate their composition, much as composite materials are used for various mechanical structures, but on a nanoscale. The films can be coated onto a surface of any size or shape, which offers more design flexibility than other drug-delivery devices that have to be microfabricated.

“The drawback to microfabricated devices is that it’s hard to coat the drug over a large surface area or over an area that is not planar,” said Wood.

Another advantage to the films is that they are easy to mass-produce using a variety of techniques, said Hammond. These thin-film systems can be directly applied or patterned onto 3D surfaces such as medical implants. Other application are foreseen in the related fields of tissue engineering, medical diagnostics, and chemical detection.

Prussian Blue

Prussian blue is also used in paints and formerly in blueprints. It was actually discovered by accident by painter Heinrich Diesbach and Johann Konrad Dippel, ironically while trying to create a paint with a red tone, in 1705, in Berlin, which is why it is also known as Berlin blue.

The list of artists who have painted with it includes Gainsborough, Monet, Van Gogh, and Picasso in his so-called Blue Period. Although it is FDA-approved for use[2], (for treatment of internal radiation contamination) when treated with certain acidic chemicals it can give hydrogen cyanide gas, which is, of course, quite toxic.

1. Kris C. Wood, Nicole S. Zacharia, Daniel J. Schmidt, Stefani N. Wrightman, Brian J. Andaya, and Paula T. Hammond
Electroactive controlled release thin films
PNAS published February 12, 2008, 10.1073/pnas.0706994105

2. Questions and Answers on Prussian Blue U.S. Food and Drug Administration Website