March 26, 2000

Manipulating molecules: Cornell group creates tiny structures for drug delivery by using old industrial method in new way

atomic force microscopy image
An atomic force microscopy image, 1 micron (millionth of a meter) square, of a polyvinylalcohol nanocomposite that might be used in drug delivery. Light areas are layers of silicates. Brown areas are chains of polymer molecules that might act to control drug flow.

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

The difference is that the Cornell engineers, working under Emmanuel Giannelis, professor of materials science and engineering, are working with 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 Cornell undergraduate student who has been helping to develop the material since last year. He presented a poster-paper on his research at the American Chemical Society national meeting today (March 27) at the Moscone Convention Center in San Francisco.

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

Giannelis 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 today moderated a panel on the subject of drug delivery at the ACS meeting 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 gellike 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."