Researchers use precision release of microspheres to deliver medicine

Scar-free tissue regeneration, precision-controlled release of ingested or injected drugs, and other medical marvels are a step closer to reality thanks to new research by ECE researchers Kyekyoon Kim and Hyungsoo Choi.

For decades, Kim’s Thin Film and Charged Particle Research Laboratory has pioneered the fabrication of microparticles for a variety of science and engineering applications. More recently—in collaboration with Choi and with the addition of electric field effects—Kim has applied his techniques to hydrogels with medical applications. The team’s latest success is a new way to make hydrogel particles “monodisperse,” that is, particles that are perfectly uniform and don’t stick together while hardening.

Water soluble, tissue-friendly hydrogels such as chitosan, starch, and gelatin are the subject of intense research surrounding their use in precision drug delivery. Kim and Choi believe their most promising application will be in tissue engineering. Hydrogel particles will carry proteins such as growth factor to injured soft tissue or to bone, giving a boost to the natural healing process. Or growth factor may be used to enhance the proliferation of stem cells.

Problem is, droplets of these materials tend to agglomerate as they harden, reducing the ability to regulate drug delivery through precise control of particle size. Potentially toxic surfactants, such as detergent, may separate the spheres but will counteract the tissue-friendliness of the hydrogel. So Kim and Choi apply an electric field that induces controlled charging of particles and subsequent Coulomb repulsion between them, ensuring that they keep a polite distance from each other while hardening. By controlling the strength of the electric field, the researchers can control the amount of separation between particles.

The new process enhances established methods that Kim has developed to fabricate microparticles of precisely controlled size and uniformity. The process begins with spraying a solution of drug and biodegradable polymer (the encapsulating material, such as hydrogel) through a small nozzle. An acoustic excitation applied at the nozzle breaks the stream into uniform droplets, much like waving the nozzle of a running hose to produce beads of water. In order to produce drops as small as five microns in diameter—much smaller than the nozzle opening—Kim uses concentric nozzles with a carrier stream introduced in the outer nozzle. The carrier stream surrounds the inner jet of solution and, combined with the acoustic excitation, produces uniform drops a fraction of the size of the inner nozzle opening.

“We can tailor the release profile of a drug by controlling the surface-to-volume ratio of the drops,” said Kim. He likened the spectrum of release profiles to the different ways one might eat sugar: “We can make it like powdered sugar that dissolves immediately in your mouth, or a lollipop that melts slowly and evenly for a long time.”

Choi’s background in chemistry complements Kim’s in physics, enabling the team to apply Kim’s techniques to new and promising, but difficult, materials. “I knew about the microparticles, and I thought, ‘Why not try the hydrogel materials, which are more challenging but suitable for protein delivery?’” said Choi. “With [Kim’s] method you can use any material, but you need tailoring of the process for each material.”

Kim and Choi, along with co-author and former PhD student Young Bin Choy, received a patent for their microparticles on December 18, 2007. The three reported their latest success with monodisperse spheres in the cover article of the April 10, 2007, issue of the journal Macromolecular Bioscience.  Choy is now a postdoctoral fellow at Georgia Tech.