IMPLANTED POLYMERS FOR DRUG DELIVERY

We have all heard that biodegradable polymers are good for the environment. But they may be good for cancer patients, too. Efforts are now under way to design polymer implants that will slowly degrade inside the human body, releasing cancer-fighting drugs in the process.

Such an implant would need several specific properties. It would have to degrade slowly, from its outside surface inward, so that a drug contained throughout the implant would be released in a controlled fashion over time. The polymer as a whole should repel water, protecting the drug within it—as well as the interior of the implant itself—from dissolving prematurely. But the links between the monomers—the building blocks that make up the polymer—should be water-sensitive so that they will slowly fall apart. Anhydride linkages—formed when two carboxylic-acid-containing molecules join together into a single molecule, creating and expelling a water molecule in the process—are promising candidates, because water molecules readily split the anhydride linkages in the reverse of the process that created them, yet the polymer molecules can still be water-repellent in bulk. By varying the ratios of the components, surface-eroding polymers lasting from one week to several years have been synthesized.

These polymer disks are now being used experimentally as a postoperative treatment for brain cancer. The surgeon implants several polyanhydride disks, each about the size of a quarter, in the same operation in which the brain tumor is removed. The disk contains powerful cell-killing drugs called nitrosoureas. Nitrosoureas are normally given intravenously, but they are effective in the bloodstream for less than an hour. Unfortunately, nitrosoureas are indiscriminately toxic, and this approach generally damages other organs in the body while killing the cancer cells. But placing the drug in the polymer protects the drug from the body, and the body from the drug. The nitrosourea lasts for approximately the duration of the polymer—in this case, nearly one month. And the eroding disk delivers the drug only to its immediate surroundings, where the cancer cells lurk.

The polymer degradation method of drug delivery is making good progress toward approval by the Food and Drug Administration.

applications. (See the vignette "Seasickness Patches.") Recently, more sophisticated technologies have emerged, such as electrotransport systems, whereby the drug is driven from a reservoir under the influence of an electric field. Such systems are being developed predominantly for transdermal drug delivery.

There are many challenges in designing polymers for controlled-release applications. These polymers must be biocompatible, pure, chemically inert, nontoxic, noncarcinogenic, highly processible, mechanically stable, and sterilizable. The polymers in use today in drug delivery are also mostly borrowed from the chemical industry and in many cases lack the exact required properties. Novel polymers designed and synthesized to provide optimal properties and characteristics will be required to take full advantage of the emerging technologies described above.

A number of controlled-release products are on the market in the United



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