Tiny needles deliver drugs painlessly.

Microscopic needles may one day join hypodermic needles and drug-loaded patches as a way to get medicines into the bloodstream. Whereas syringes hurt and patches work only for small molecules, painless microneedles could deliver medicinal proteins and other large molecules through the skin, say developers of the technology.

Mark R. Prausnitz of the Georgia Institute of Technology in Atlanta and his colleagues describe new methods for making arrays of both solid and hollow microneedles, as well as the first proof of the efficacy of hollow microneedles. They report their findings in the Nov. 25 Proceedings of the National Academy of Sciences.

The solid needle would work by riddling the skin with tiny holes, allowing drugs from an overlying patch or on the needles themselves to seep into the body.

To make it to the clinic, however, microneedles will need to be mass-producible and cheap, says Prausnitz. His team used microfabrication and etching techniques to make molds hosting up to 1,000 solid microneedle forms in a thumbnail-size piece of silicon, metal, or polymer. Filling the forms with metals or polymers resulted in hair-thin needles no longer than the width of the period at the end this sentence. Needles of these dimensions don't cause pain, since they can avoid nerves, but they also aren't as strong or penetrating as larger needles.

"There are various trade-offs between getting needles to go in, getting the needles to go in without hurting, and delivering enough of the drug," says Prausnitz. Microneedles would be especially beneficial for people with diabetes and others who need frequent injections, he notes. But Prausnitz suspects that the "real opportunity for microneedles is in the process of extended drug delivery"

To realize that possibility, the researchers have developed ways of fabricating hollow microneedles through which drugs can flow at controlled rates. The researchers have made such structures in several ways, including drilling microscopic holes through silicon and electroplating a thin layer of metal on only the inner surfaces of the needle forms the team created.

As a simple test of the efficacy of hollow microneedles, the scientists pulled glass pipettes to create microscopic tips and used them to inject insulin into diabetic rats. The treatment lowered the animals' blood sugar concentrations for at least 5 hours.

Showing that hollow microneedles can deliver drugs to animals "represents an important milestone in the development of this technology" says Samir Mitragotri of the University of California, Santa Barbara.

Several biotechnology companies are developing microneedles for use in people. Robert Gale of Alza Corporation in Mountain View, Calif., notes that his company is developing solid, drug-coated microneedles, which the company hopes to market in 2 to 5 years.