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Smart gels. Physicist Zhibing Hu works on new medicine delivery system. By Rufus Coleman

The toughest part of using any medication is remembering when to take it and how much to take. That’s why Zhibing Hu, Ph.D., professor of physics at the University of North Texas, is developing a type of gel with microscopic particles that do all the work for you.

Using hydrogels — water-based, gelatin-like polymers that can be programmed to expand and contract in reaction to temperature — Hu has created a self-regulating delivery system for medicine.

When fever raises the body temperature, the tiny particles of the hydrogel contract and squeeze out medication. And when fevers subside, the particles expand to hold the medication in.

Because hydrogels are highly absorbent, they can hold huge amounts of medicine. The water-based gels also are extremely compatible with human beings — they’re nontoxic and easy for the human body to break down.

Closeup of a hypodermic  
UNT physics professor Zhibing Hu is developing a system that uses hydrogels to deliver medicine within the body. The polymers’ super-absorption abilities may also make them useful to the diaper industry.    

An individual could potentially be given one injection of a hydrogel filled with medication for an ailment and receive its benefits through the course of the illness without a second thought.

Hu also hopes to develop biodegradable hydrogel devices that can be implanted to medicate an illness. Once the device has completed its task, it can be broken down and absorbed by the body.

Both the injection and the device could work for as long as a month or as short as a single day.

Absorbency and flexibility

While hydrogels and time-released medications aren’t new inventions, Hu’s method of creating hydrogels with this kind of precision could have a major impact on the drug industry.

Already he has received grants totaling nearly $1 million from the National Science Foundation, the U.S. Army Research Office, the Texas Advanced Technology Program and Access Pharmaceuticals Inc. in Dallas to perfect hydrogel systems of drug delivery.

Hu is one of only a hundred scientists in the world who develop hydrogels. He’s been studying them since 1990, and his work has been profiled in Nature, a weekly international journal of science; the Encyclopedia Britannica’s 1999 Yearbook of Science and the Future; Science magazine; and numerous other notable science journals.

Currently, Hu’s energies are dedicated to perfecting his hydrogel drug delivery systems, but due to the many ways in which they can be programmed, hydrogels have numerous applications. The gels can respond to light, pH balances and electric fields in addition to temperatures.

One sponsor of Hu’s research, the Kimberly Clark Co., hopes to use the super-absorption abilities of hydrogels in diapers. Future applications could mean, for instance, that when diapers are warm and wet, hydrogels inside will instantly begin absorbing liquid. When the baby is dry again, the hydrogels will respond to the cooler temperature, expanding and sealing in the wetness. Kimberly Clark aided Hu and his team in gaining two U.S. patents.

Display of hydrogels
Hydrogels can be programmed to expand and contract in reaction to temperature.  

Because of hydrogels’ ability to expand and contract and their compatibility with the human body, the gels could also serve as artificial muscles. Hydrogels can be programmed to react to electrical impulses like human muscles do. Their ability to expand and contract would allow them to curl an arm and extend it again.

"These hydrogel muscles could be used to make artificial limbs more efficient or literally to replace a damaged muscle in a human arm," Hu says.

Some gels also have shape memory, curling into a predetermined shape in response to an environmental change, such as a change in temperature. A straight strip of gels that includes both responsive and non-responsive gels bends one way or another when only the responsive gels react.

Cooking up crystals

But Hu believes his work in medicine delivery will have the most impact.

Hu uses a device that allows him to see the nano-sized crystals  
Hu uses a device that allows him to see the nano-sized crystals. The space between them determines the rate at which medication is released.    

Initially, his research focused on creating a means to measure and predict the rate at which the hydrogels would release medication.

To do this he had to take hydrogels, which on a microscopic level are shapeless and difficult to measure, and turn them into something with constant and precise shapes that could be measured more easily.

By chemically creating a way to organize and stabilize the hydrogel molecules on a nanometer level (a billionth of a meter), Hu produced crystal hydrogel structures. This procedure also allows him to program the rate of release for a medication with precision.

"The whole process requires a unique combination of chemistry to create and sort the crystals and physics to see if we’ve achieved the desired effect by measuring
the rate of release for the hydrogel nanoparticles," Hu says. "I must use a unique team of physicists and chemists."

In the first part of the process, Hu creates hydrogel nanoparticles by mixing chemicals and water with nitrogen. The resulting hydrogel nanoparticles have a uniform, spherical shape.

He then uses a centrifuge to separate the hydrogel nanoparticles from the mixture of water and chemicals. The nanoparticles sort themselves into an organized crystal form, and Hu stabilizes the crystal by chemically bonding the nanoparticles together in the centrifuge.

He uses a device that allows him to see the nano-sized crystals, which are iridescent, soft, elastic and water-swollen like gelatin, and measure the spaces between the particles. The spaces determine the rate at which medication is released.

By altering the formula that causes these particles to bond, Hu can change the spaces between them and the release rate of medication.

"It’s like cooking up a recipe," he says. "You have to perfect the recipe to achieve a specific goal, and that takes a lot of experimenting. But once you’ve got it, the hydrogels efficiently and safely perform their job."

Hydrogels deliver

Once Hu and his research team of graduate students have the recipe right, the hydrogel crystals are put in a tube with the medication to absorb it.

Then these particles are bonded together once more in the centrifuge.

This process, along with the natural properties of the hydrogels, allows Hu to program hydrogel particles to regulate and distribute medication for patients.

A variation on the process can make the hydrogels sensitive to pH balances. So, for instance, hydrogel particles would be smart enough to wait until they are out of the stomach where pH levels are low and into the intestines where pH levels are neutral before releasing medication. This could prevent some unpleasant side effects, like a stomachache.

It is also an early step toward programming smart gels to deliver medication to specific parts of the body.

Right now, all of these applications are in their infancy, but in time Hu expects that his intelligent nanostructured hydrogels will create safer, more efficient products with a huge impact on our society.































































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