CU researchers work to create tiny mechanisms for the delivery of drugs

Cornell undergraduate researchers Ruth Chen and Stephen Cypes presented their posters March 27 at the American Chemical Society's annual meeting in San Francisco's Moscone Center. They are shown above in front of Chen's poster on thermosensitive nanocomposite gels. Stuart Brinin

By David Brand

By using a process analogous to the way that tires and refrigerator doors are made, Cornell materials engineers are hoping to find a new mechanism to deliver drugs to the human brain or bloodstream.

The difference is that the engineers -- some of them Cornell undergraduates working at the forefront of biomaterials research -- are using inorganic fillers, not in large clumps as in industry, but at close to the molecular level. By inducing chains of polymer molecules to slide between silicate layers, each a few atoms in thickness, they have produced a material, called a polyvinylalcohol (PVA) nanocomposite, that holds promise as an injectable drug delivery system.

"These biorelevant nanocomposites are important not only for drug release but perhaps also for tissue engineering," said Stephen Cypes, the undergraduate who has been helping to develop the material since last year. He presented a poster-paper on his research at the American Chemical Society's national meeting Monday in the Moscone Center in San Francisco.

Nearly two dozen Cornell researchers gave papers at the society's 219th annual meeting, which began March 26 and ends Friday, March 31.

Cypes, who is from Darnestown, Md., comes to cutting-edge research at a very young age. He is only a sophomore, majoring in chemical engineering and studying under the Cornell Presidential Research Scholars Program, which supports the research. Also presenting a poster-paper at the ACS meeting was Cornell junior Ruth Chen from Toronto, also a research scholar. Her research is in the area of developing new thermosensitive nanocomposite gels. Applications for these materials include drug delivery, enzyme carriers and chemical valves.

Emmanuel Giannelis, professor of materials science and engineering, who heads the research group that includes Cypes and Chen, noted that his work on drug-delivery materials has been influenced by his colleague, Cornell chemical engineering professor Mark Saltzman, an authority on the subject of drug delivery, who has developed pea-size pellets of a biocompatible polymer that could be used to deliver drugs to the body through implantation. Saltzman, who is Cypes' academic adviser, said of his student's work: "This is an important innovation in the development of new materials for drug delivery. Most research currently uses a few polymeric materials that are known to be biocompatible; usually you are stuck with the properties of the materials that are acceptable biologically. This work shows a way to take the same biologically acceptable materials and alter their permeability and mechanical properties, which should open the door for additional applications."

At the ACS meeting, Saltzman moderated a panel on the subject of drug delivery and presented an overview of the subject taken from his forthcoming book Drug Delivery, which is being published later this year by Oxford University Press.

"The Saltzman group has expertise in taking polymers, impregnating them with drugs and implanting them into animals," said Giannelis. "We asked, can we take these materials and improve them with better control of their drug-release characteristics? They also need better mechanical properties -- they are, for example, very brittle."

What Giannelis and his team envision is a microscopic polymeric sphere that could be impregnated with drugs and injected into the body where it would slowly release the needed drug before biodegrading into the body's tissue.

Giannelis' idea was to take a very old industrial idea, using inorganic particles, such as talc, as filler, but reducing the material almost to molecular scale to create what he calls "nanofillers." To do this, he took advantage of the natural structure of silicates, which under a microscope have a layered appearance like a pack of cards. The atomic bonds between the layers are weak, allowing them to be slid against each other or to be opened up. Using a basic mixing and melting method, the researchers were able to introduce molecular chains of PVA, which is a nontoxic and biodegradable inorganic polymer, between the layers, forming a layered, latticed structure. "This nanostructured material has a lot of interfaces and for the first time we started seeing dramatic changes in the mechanical and physical properties," said Giannelis.

Once a drug was incorporated into the material, said Giannelis, the PVA would create physical barriers to slow down and impede the flow of the medication. The layers also would interact with the drug to create a chemical barrier. "In this way you could change the amount of the inorganic material to create fewer barriers and speed up the release, or you could manipulate the chemistry. You have two knobs in your hands," Giannelis said.

Because the material is hydrophilic, it takes up water and swells to create a gel-like material through which molecules can easily flow. "Ideally you would want a material that could absorb the most water possible because then you could include the most drug and have it release as slowly as possible," said Cypes.

"We have demonstrated that the transport of small molecules can be controlled and changed," said Giannelis. "The next step is to incorporate active agents and watch how they are being released."