By Julia Ferrante
LEWISBURG, Pa. -- Brandon Vogel was looking for a quicker way to make degradable polymers when it occurred to him that a microwave oven might do the trick.
A graduate student at the time, Vogel was conducting experiments on plastics that break down under certain conditions. Just making the material for those experiments, however, took about two weeks. "I figured if a microwave can cook food evenly and quickly, it might be a good method to heat reactions." said Vogel, now an assistant professor of chemical engineering at Bucknell University.
So he decided to give it a try.
"We had a spare microwave in the garage of my house in graduate school," Vogel recalled. "I had no idea how long I should heat the reaction in the microwave the first time I tried it. I put it in for two minutes then walked away -- just in case. I came back into the garage, and a polymer had formed in the vial. After some optimization of the reaction, I managed to make the polymer in six minutes."
The process, called microwave synthesis, now is done by his students in more controlled, research-grade machines, but the discovery has led to several other research projects that could have far-reaching applications in medicine. Vogel, who came to Bucknell in 2007 after working at the National Institute of Standards and Technology in Washington, D.C., has published several papers on the subject and has two patents pending.
A visiting professor at Bucknell last year, he was hired for a tenure-track position this year. His research group is working to synthesize new biomaterials to detect, target and treat disease.
One of the projects Vogel is working on at Bucknell is to develop new degradable polymers that, when mixed with pharmaceutical drugs, can control the release of those drugs. These polymers can protect the drugs from harsh internal body conditions and extend the release time so patients may take fewer doses less frequently. Diabetes patients could, for example, take insulin just once a month or even once a year rather than several times a day.
Breaking it down
Polymers are long chain molecules made up of monomers and connected by chemical bonds. Items such as garbage bags, bottles and phones are made up of polymers. The physical properties of the plastics are determined by how the monomers are connected and what chemical structures the monomers contain. Garbage bags and plastic bottles, for example, have monomers that are strung together by strong chemical bonds, making them difficult to break down, which is why they remain in landfills for such a long time.
Degradable polymers have weaker bonds that cause them to break apart when they come into contact with external stimuli such as heat, light or moisture. A commonly used degradable polymer is polylactic acid, which often is used to make salad container packaging.
"When water comes into contact with hydrolytically degradable polymers, it breaks the bonds of the monomers and causes the length of the polymer chains to shorten," Vogel said. "Eventually, you are left with the monomer."
How it works
The process can work well in developing controlled-release medications, Vogel said.
"What we do in drug delivery is take a polymer that can degrade and put a drug in it," he explained. "By changing the chemistry of the monomers and chemical bonds, we can change the time it takes for polymers to degrade from hours to years. We can even change the mechanism by which they degrade."
Degradable polymers generally are characterized as bulk- eroding or surface-eroding. Bulk-eroding polymers such as polylactic acid degrade when they swell with water -- expanding like a sponge does -- and break apart throughout their "bulk." Surface-eroding polymers prevent water from swelling inside them, so they only degrade at the surface, like a piece of hard candy.
Finding a better way
Creating controlled-release forms of insulin presents challenges because insulin is a type of drug that can become ineffective when exposed to extreme pH or body temperatures, Vogel said. Manufacturers need to find better ways of keeping the drug in its active form until the body needs it.
"Insulin has a certain shape, and this shape dictates its ability to act as a therapy," Vogel said. "If it gets out of shape, it doesn't work anymore. When physicians inject insulin into the body, much of the protein denatures, or loses its shape, because it is such a delicate protein. This fact must be taken into account, so additional insulin is added in the injection to make sure the active insulin is at a therapeutic level. It ends up being a waste of insulin and can pose risks to the patient."
Vogel and his student researchers are trying to solve this problem by making bulk-eroding polymers into surface-eroding polymers.
"Surface-eroding polymers are expensive and difficult to make in comparison to bulk-eroding polymers," he said. "As bulk-eroding polymers degrade, they swell with water, and when the polymers break down into monomers, the monomers get trapped inside the polymer.
"Since these monomers usually contain acid, the pH inside the polymer can drop very quickly, causing any protein inside a drug-delivery device to denature," Vogel said. "This could all be avoided by making the polymer surface-eroding instead of bulk-eroding."
Another benefit of surface-eroding polymers is that they maintain their mechanical strength as they degrade.
"This is an advantage for items like degradable plastic containers and degradable plastic forks that need good mechanical strength," he said.
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