Biodegradable microneedle particles improve drug delivery through the skin

Your skin is remarkably good at keeping things out of your body.

Typically, that's a positive. It becomes an issue when medicine needs to get in.

Swallow a pill to treat a skin condition, and the medicine enters your stomach, moves into your bloodstream, and travels throughout your body - all to reach a problem in your skin.

Applying the drug directly seems simpler. But the skin's outer layer blocks most medicines meant to treat it.

Mark Prausnitz, a Regents' Professor, Regents' Entrepreneur, and J. Erskine Love Jr. Chair in Georgia Tech's School of Chemical and Biomolecular Engineering, has spent years trying to get medication through that barrier. He says his solution looks a little like a tiny spiny creature or a centuries-old weapon.

Like the ball and chain of medieval times, with all those spikes sticking out of the ball. Or like a porcupine."

Mark Prausnitz, a Regents' Professor, Regents' Entrepreneur, and J. Erskine Love Jr. Chair, School of Chemical and Biomolecular Engineering, Georgia Tech

Only much, much smaller.

Prausnitz calls them STAR particles because tiny microneedles project from each particle like the points of a star. Mix them into a cream or gel, rub them across the skin, and they create microscopic openings that give medicine a way through.

Ditching the patch

The idea grew out of microneedle patches, which are already used to help drugs penetrate the skin. But patches are best suited to small areas. But conditions such as eczema and psoriasis can affect broad or irregular parts of the body where Prausnitz said patches would be impractical.

STAR particles ditch the patch. Mixed into a cream or gel, they can be rubbed wherever they're needed. Their microscopic points puncture the skin's outer barrier, creating openings that help drugs get in.

"Just that rubbing action on your skin causes these particles to roll and slide around and poke little holes in the skin," Prausnitz said.

Those openings allow the medicine in the cream or gel to be absorbed over time. In one small human study, earlier ceramic STAR particles helped a topical anesthetic take effect faster and reduce sensation more than the anesthetic used alone.

Separate tests focused on tolerability. The particles caused mild redness, but it faded. Participants described tingling rather than pain or discomfort.

"You can barely even tell," Prausnitz said of the earlier particles. "If you look very closely, you can see just faint redness on the skin. But if you look from a distance, you can't even tell it's there."

But those particles were made from titania, a material that is safe but isn't biodegradable. Once they have done their job to deliver drugs into the skin, they have an uncertain fate afterwards. 

No one has found evidence they cause harm. Still, Prausnitz wondered where they might end up after use. In an eye? On a child? Somehow impacting the environment? Those questions drove the redesign.

Designed to disappear

Prausnitz and his team created new STAR particles with three materials that break down after use. One is the same substance used in dissolvable stitches, which is a biodegradable plastic that can be made from corn. Another is based on cellulose, which is a major component of essentially all plants. The final is an additive often used in candy and other foods. All three made the tiny openings needed to help compounds pass through the skin.

The strongest result involved copper tripeptide-1, a skincare ingredient. Prausnitz reported good results with methotrexate, which is used to treat psoriasis, and with tacrolimus, which is used to treat eczema. 

With STAR particles, nearly 37 times as much entered the skin as without the particles That doesn't mean it was 37 times more effective. The study measured drug delivery into the skin, not treatment results. And the biodegradable particles haven't been tested in people yet.

Prausnitz said some drugs that might otherwise be useful for skin disease have been "thrown in the trash or stuck on the shelf" because of the side effects caused when they circulate throughout the body. Drug delivery directly to the skin using STAR particles could reduce those side effects. 

He has also said STAR particles might one day deliver anti-aging treatments without injections or harsher procedures. Those cosmetic uses, however, were not evaluated in this study.

For patients, using STAR particles could feel much like applying an ordinary cream or lotion: Rub it on. Feel a little tingle.

"Users don't really know or care that STAR particles are in there," Prausnitz said. "Your experience is a familiar one."

The study was published in the journal Advanced Healthcare Materials.