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Langer reviews polymer drug-delivery work in Killian Lecture

When, as a postdoctoral fellow in 1974, Dr. Robert S. Langer first became interested in drug-delivery polymers, no one believed this method of slowly releasing medicines into the blood through a plastic implant or microsphere could ever be used with large molecules. Trying to squeeze the large molecules developed by genetic engineering companies through a thin polymer matrix would be like trying to squeeze a baseball through a screen, most believed.

It took years and a lot of hard work, but Dr. Langer, the Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering and the recipient of 26th Killian Faculty Achievement Prize, proved them wrong. He discussed this work at the Killian Lecture on March 11.

Professor Langer found that if you put a protein in the polymer matrix in a certain way, it leaves behind pores that would allow even the biggest molecules to pass through. What's more, with a little jiggering, you could get the molecules to pass through when they were needed.

"The pores have tight constrictions and are very winding and tortuous, slowing the rate at which molecules can pass through," he said. "Using various approaches in chemical engineering and materials science, the pore structures can be controlled, predicted and even tailor-made to achieve different release rates."

Systems based on Professor Langer's research are now used to treat patients with advanced prostate cancer, brain cancer, endometriosis and many other diseases. The brain cancer procedure, which saves the liver, kidney and spleen from damage by a potent drug, is the first new treatment for brain cancer approved by the US Food and Drug Administration (FDA) in more than 20 years.

Besides pioneering the use of polymers as drug-delivery vehicles, Professor Langer also discovered that polymeric systems could be used for tissue engineering. By fusing mammalian cells with synthetic polymers, he and his colleagues have created skin, cartilage, tendons, bone, nerves and even a tube lined with working intestinal cells in animal models.

Artificial skin made with this method is now approved by the FDA. An artificial liver also is being studied. Working with Dr. Jay Vacanti, head of surgical transplantation at Boston Children's Hospital, Professor Langer created scaffolding of biodegradable polymers that would support cells and allow them to be nourished, proliferate and function just like cells in the body.

"We wanted to engineer a new organ in situ by placing functioning dissociated cells onto biodegradable polymers and culture them outside the body," he said. They would then place the artificial organ into the patient, where it would be hooked up to the blood supply and grow.

Others, including Linda G. Griffith, the Karl Van Tassel Associate Professor of Chemical Engineering and a former Langer postdoctoral associate, have used these procedures to create an artifical ear out of cartilage. Cartilage cells are multiplied and placed on a polymer in the shape of a human ear. This method can provide replacement parts for those born without complete ears or noses or who need reconstructive surgery following an accident.

In the future, drug-release systems may be able to provide a steady supply of insulin to diabetics; slow release of vaccines such as that for tetanus, which need repeated booster shots; or for an AIDS vaccine. The release of growth factors may some day help build new supplies of blood vessels, while gene therapy delivery systems may be used for various applications such as controlling cell growth within blood vessels to prevent blockage.

The delivery of genes and other agents to blood vessels has been pioneered by Elazer R. Edelman, the Thomas D. And Virginia W. Cabot Associate Professor Of Health Sciences and Technology and another former Langer postdoctoral associate.

Professor Langer noted that the field has come a long way since 1974, when no one believed that polymers could be used to deliver peptides and proteins. In 1989, the FDA approved a polymer-based treatment for advanced prostate cancer that delivers a hormone that could not be administered through a pill.

"It is my hope that as chemical and biomedical engineers and materials scientists continue to work with clinicians and biologists, we can begin to solve some of the terrible problems that affect people, that we can relieve suffering, and that we can prolong life," Professor Langer said.

A version of this article appeared in MIT Tech Talk on March 18, 1998.

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