The right drug at the right time
SMART plastic films programmed to release a precise sequence of drugs are poised to revolutionise drug delivery thanks to a breakthrough in polymer chemistry. The films could be used to coat implants such as artificial hips and tissue scaffolds to deliver phased shots over a period of hours or weeks.
Simple drug-releasing coatings are used in devices such as the stents used to keep arteries open after surgery. The coating continually releases a drug that inhibits the cell growth that can block an artery. But programmed, timed release of a sequence of drugs could have much broader applications.
The idea has been pursued since 1997, when Gero Decher of Louis Pasteur University in Strasbourg, France, devised a method for depositing very thin polymer films on objects of any shape. The hope was that drugs embedded in these films would be released slowly as the layers broke down in the body. Programmed delivery would simply be a question of varying the thickness of the layers and building in barriers to delay release.
But chemists have battled against a major problem: no matter how thick or thin the layers, the drugs tend to leach out all at once. "Ideally you would like to be able to peel them off one by one," says David Lynn, a polymer chemist at the University of Wisconsin-Madison, who presented his work at the annual meeting of the American Chemical Society in Washington DC last week.
In Decher's layer-by-layer approach, an object is dipped alternately into vats of negatively and positively charged polymers. If a drug is added to these polymers, it will become embedded in the layer, and a barrier layer on top should seal it in. But because the polymer chains in the barrier are held together only by electrostatic forces, water can penetrate, allowing the drugs to leach out.
Now that problem has been solved. Paula Hammond and Kris Wood of the Massachusetts Institute of Technology, together with Lynn, cross-linked the polymer chains to form a mesh that can delay water penetration and the release of any drugs.
The team has used the technique to precisely control the release of heparin and dextran sulphate, both sequentially and simultaneously. "We have tuned the polymers to degrade at different rates by changing the composition of the barriers that separate the layers," says Hammond.
Another team that also presented its work at the meeting used a similar method to shuttle DNA fragments into cells, a technique that could be used for gene therapy. Jean-Claude Voegel of INSERM (National Institute for Health and Medical Research) and Pierre Schaaf of the Charles Sadron Institute, both in Strasbourg, also announced plans to embed vesicles containing two types of drug that become active when the polymer layer breaks down releasing the two chemicals. "It's a nanoreactor built into a film," says Voegel.
Hammond thinks the technique could be used in humans if animal tests are successful. "Our first target is to coat bone implants," she says.
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