Tiny microspheres release drugs slowly.

The efficacy of many drugs hinges on their carefully timed delivery into the body. Some work best when administered continuously, while others prove most effective in repeated small doses.

Jeffrey L. Cleland, a chemist at Genentech in South San Francisco, and his colleagues have developed tiny capsules that slowly release compounds for specific periods of time. The scientists can design the beadlike microspheres to deliver a drug continuously or in pulses over a span ranging from a few hours to 6 months, Cleland said last week in San Francisco at a meeting of the Materials Research Society.

Made from poly(lactic-coglycolic) acid, already used safely in sutures that dissolve in the body, the microspheres carry delicate proteins and hormones for long periods without reducing their effectiveness -- a problem that plagues other slow-release drug delivery systems, Cleland said. Measuring 10 to 40 micrometers, the tiny beads can be injected with an ordinary syringe.

The team sees the microspheres as most useful for drugs that patients need continuously and must inject frequently, such as insulin for diabetes or human growth hormone for dwarfism. Certain vaccines requiring sequential injections or boosters also make good candidates for microencapsulation, as do drugs to treat cancer or chronic illnesses -- especially if the compounds cause toxicity in large doses or single injections.

To measure the release rate, the scientists entrapped a variety of agents in the microspheres and injected them into animals, ranging from mice to monkeys. Vaccines under investigation include ones for cholera, diphtheria, tetanus, hepatitis B, and rabies. The researchers are also testing human growth hormone, ordinarily injected daily or three times per week. In rhesus monkeys, the scientists find that injected microspheres release the hormone continuously for up to 1 month.

To use microspheres as potential immunity boosters against AIDS, Cleland's team has implanted in the capsules protein fragments from HIV-1 combined with an immunity-stimulating agent, QS-21. When injected into baboons, the two formulations together "exhibited the highest neutralizing antibody response to date," they report.

"For some formulations, the biological response was greater for the [microsphere-encapsulated] proteins than for the water soluble forms," says Cleland. "In the future, these protein formulations will be tested in human clinical trials and, if successful, will reach commercial use within the next 5 to 7 years."