2002

Medical microspheres provide precision-release drug delivery

James E. Kloeppel, Physical Sciences Editor
(217) 244-1073; kloeppel@uiuc.edu

4/9/02

CHAMPAIGN, Ill. — The elusive goal of controlling the release rate of encapsulated compounds for the precise delivery of drugs over a prolonged period is finally within reach.

At the University of Illinois, professor of electrical and computer engineering Kyekyoon (Kevin) Kim, professor of chemical engineering Daniel Pack, and graduate student Cory Berkland have developed a method for making drug-encapsulated, biodegradable polymer microspheres that provides precise control over sphere size and shell thickness.

With their precise microspheres, the researchers have the ability to control the drug delivery kinetics – the rate at which a drug is released to the body – and to create single-shot vaccines that could improve patient comfort and compliance.

To create uniform microspheres, the researchers begin by spraying a solution of biodegradable polymer, organic solvent, and the drug to be encapsulated through a small nozzle. "Left alone, the resulting stream would naturally break up into droplets, like water spraying from a garden hose," Kim said. "But the droplets would form in random sizes."

To produce uniform droplets, the researchers vibrate the nozzle with a piezoelectric transducer. "This launches a wave of acoustic energy along the thin liquid jet, which develops bulges – resembling sausage links – that snap off as droplets at a controlled rate," Kim said. "Shaking the nozzle at a defined rate is what makes the spheres all the same size."

To make even smaller droplets, the researchers use a coaxial nozzle to surround the polymer jet with a faster moving carrier stream. The carrier stream pulls on the polymer solution, stretching it into an even narrower stream that creates tinier droplets. By varying the flow rate and the frequency of the vibration, the researchers can precisely control the size of the resulting spheres.

By combining the acoustic activation and carrier stream techniques, the researchers have fabricated uniform microspheres with diameters ranging from 5 to 500 microns (by comparison, a human hair is about 100 microns in diameter). With a more sophisticated nozzle assembly, they have also created similarly sized microcapsules that consist of a drug core surrounded by a biodegradable polymer shell.

"Drug release rates depend very strongly on the size of the spheres or capsules containing the drug," Pack said. "Larger microspheres generally release encapsulated compounds more slowly and over longer time periods."

Microcapsules, on the other hand, can be made to release their payload only after the shell has dissolved to the point of rupture. Therefore, by varying the shell size and thickness, the researchers can control the time delay for drug release.

"For many drug delivery applications, you would like to have the drug released at a constant rate," Pack said. "This is very difficult to achieve with conventional microspheres. But by mixing microcapsules of different sizes, we can generate a constant rate of release over a relatively long period of time."

The researchers demonstrated their constant-release kinetics with both a model drug compound (rhodamine B) and with piroxicam, a non-steroidal anti-inflammatory drug commonly used to treat inflammation associated with arthritis.

Such controlled-release drug delivery would be especially useful for drugs that require multiple daily injections and for vaccinations that require additional booster shots at timely intervals. "Single-shot vaccinations could increase both patient comfort and compliance," Pack said. "They would also dramatically reduce the number of injections required when inoculating Third World nations against infectious diseases or inoculating large populations against a bioterror attack."

While the researchers have focused their efforts on drug delivery, the technology they developed has many other potential applications, from producing tiny uniform balls of solder for packaging integrated circuits to creating hollow, lightweight ball bearings for aircraft, spacecraft and satellites. The researchers have applied for a patent.

Pack will describe the making of microspheres and discuss their drug-release kinetics at the American Chemical Society national meeting, to be held April 7-11, in Orlando. His talk will take place at 2:30 P.M. on Tuesday, April 9, in Room 102B of the Convention Center.