Multilayer film provides drugs on demand

Biomaterials

March 7, 2008

Controlled release of drugs from small implanted biomedical devices could reduce the doses given to patients, or lessen whole-body exposure to drugs needed at specific sites, such as chemotherapeutics that may have toxic side effects.

Now researchers at Massachusetts Institute of Technology (MIT) and the University of Rochester have developed a multicomponent, multilayer film that releases embedded compounds in controlled amounts in response to a small applied voltage [Wood et al., Proc. Natl. Acad. Sci. USA (2008) 105, 2280].

The team constructed multiple tetralayers of alternating positively and negatively charged materials on glass substrates coated with indium tin oxide (ITO). Each tetralayer is made of positively charged linear poly(ethylenimine) (LPEI), negatively charged Prussian Blue (PB) nanoparticles, more LPEI, and negatively charged ¹⁴C-labeled dextran sulfate (¹⁴C-DS).

Prussian Blue is a nontoxic compound approved by the US Food and Drug Administration and ¹⁴C-DS is a model drug.

“When the drug-containing films are made, they are constructed by forming a complex of positively and negatively charged materials in an alternating deposition,” says Paula T. Hammond of MIT. The film is held together by the electrostatic charge attraction between the positive and negative components, she explains.

The controlled drug release occurs by destabilizing the film with an applied bias. When a voltage of 1.25 V is applied, the PB nanoparticles lose their negative charge.

“Once all the negative charge on the particles is removed, the film begins to fall apart and dissolve into the surrounding medium, releasing drug,” says Hammond. Using a 30-tetralayer film, the researchers measured the release of microgram quantities of ¹⁴C-DS when the oxidizing potential was switched on for several minutes.

“When the electric field is removed, the charge returns to the PB nanoparticles, the film becomes stable again, and drug release is immediately stopped,” Hammond notes. The team is currently focusing on in vitro experiments on delivery of cancer drugs.

Mark E. Greene