In a move that could spell disaster for the lollipop industry, scientists have reported progress in designing pain-free vaccines that people might be able to use at home. Someday that might mean fewer jabs at the doctor's office — and fewer crying kids needing a sweet to comfort them.
The Band-Aid-like patches, coated with microscopic needles, generally don't hurt. Moreover, they may actually work better at delivering vaccines and some medications, according to recent research.
Mark Prausnitz, a bioengineer at the Georgia Institute of Technology in Atlanta, hopes that painless, easy-to-use vaccines will mean that more people get them. Take flu shots: Although the government recommends that nearly everyone more than 6 months old get a seasonal flu vaccine, fewer than 40% of adults at low risk for flu and fewer than 60% at high risk reported getting the vaccine in 2008.
Prausnitz envisions an easy-to-use patch that people could pick up at the pharmacy or receive by mail and use at home. "I think that many more people would get their flu [vaccine] if they could do that," he says.
In addition, Prausnitz notes, many newer drugs don't work if swallowed or applied topically, making injections the only option. But many people are needle-shy, and even if they aren't they may not perform the procedure correctly at home.
So for 15 years, researchers have been developing adhesive patches bristling with needles that are so tiny they can't be seen by the naked eye and are barely noticeable when they slide into the skin. (To avoid even evoking the thought of sticky, poky needles, companies prefer terms such as "micropillar" or "microprojection.") Prausnitz is focusing on vaccines, most recently flu; other scientists are developing patches for various medicines.
Microneedle patches are about the size of a postage stamp and hold hundreds of miniscule needles, each less than a millimeter long. They feel "like 400-grit, fine sandpaper," says Pete Daddona, chief scientific officer at Zosano Pharma Inc., in Fremont, Ca., which is working on microneedle delivery for several drugs, including one for treating osteoporosis.
Though skin is approximately 2 millimeters thick, the outermost barrier is much thinner. Once through it, the microneedles are within the skin's wet interior, where vaccines can reach the immune system and medicines can easily get into the bloodstream.
"This is going to be a very straightforward, user-friendly system," Daddona says. "People can just pick it up and put it on, without much direction."
Engineers make microneedles out of metals or polymers; Prausnitz's latest version is made of a water-soluble substance, so it dissolves in the body. He and colleagues at Georgia Tech and Atlanta's Emory University reported on their experiments with the device in the journal Nature Medicine this month.
First the researchers mixed the water-soluble compound that makes up the needles with flu vaccine. Then they molded it into tiny spikes and attached them to a patch. They affixed the patches to mice for 15 minutes, during which time the needles dissolved away, releasing the vaccine.
One month later, when the researchers exposed the mice to a lethal dose of flu, animals receiving the patch remained healthy, as did another group of mice receiving a traditional flu shot. A third group, of unvaccinated mice, wasted away in less than a week.
The technology "has a huge potential to impact how we deliver vaccines," says Samir Mitragotri, a chemical engineer who studies vaccine delivery alternatives at UC Santa Barbara. Mitragotri was not involved in the Nature Medicine study.
The skin, Mitragotri says, is actually an ideal target for vaccines because protection is its job: It's full of immune cells ready to deal with an infection or, in this case, react to a vaccine. But because it's so thin, doctors rarely target it: "It is very difficult to get a conventional needle and deliver the vaccine into the skin," Mitragotri says.
"Microneedles can do that," he added.
Indeed, microneedles in the skin appeared to work better than injections in the muscle in the mouse study. Three months after vaccination, the researchers exposed the mice to flu particles, which the animals inhaled. Within four days, the patch-vaccinated animals had destroyed 1,000 times more of the virus in their lungs than the injection-vaccinated mice.
Prausnitz plans to do a small study of the flu vaccine patch in people, initially just to make sure it's safe. He is also working on microneedle vaccines for polio and the measles.
He has already shown that people who use the microneedle patch don't find it painful. In the Clinical Journal of Pain in 2008, Prausnitz and colleagues reported on a pain study with human volunteers. Most people receiving a regular injection said it hurt, Prausnitz says. That wasn't the case for most of those who got the patch, although they did say they could feel it.
In addition to vaccines, many other drugs currently come in needles. Zosano, among other companies, is working to change that. Its system is an array of titanium microneedles, shaped like arrowheads, that have a dry medicine coating. Once inside the skin, the medicine dissolves away from the needles.
Daddona says they leave only a bit of redness when removed.
Zosano's lead patch candidate is a drug for osteoporosis — teriparatide, a lab-made version of the human parathyroid hormone. Teriparatide is already available for osteoporosis but requires daily needle sticks.
The company recently completed a trial comparing teriparatide-coated microneedles with standard injections, which was published in January in the Journal of Clinical Endocrinology and Metabolism. For six months, 165 women with osteoporosis received, daily, either injections, the microneedle patch with medicine or the patch with a placebo. Researchers found increased bone mineral density in the spines of women who received the drug in either form.
The microneedles appeared to provide more benefit than the single long needle, the scientists reported: When the researchers examined bone density in another site, the hipbone, they found that microneedle delivery increased mineral content while injections did not.
This could be because teriparatide works best when it's given as a brief pulse, Daddona says. With injections, fatty tissue at the injection site slows down the drug's spread. But with microneedles, the medicine reaches the bloodstream faster.
Zosano is in discussions with the Food and Drug Administration to plan a larger trial of the osteoporosis treatment. The company also is developing patches for several other drugs, including erythropoietin for anemia in people with kidney disease.