If you have a lemon, make lemonade

When an experiment in his lab took an unexpected turn, W. Mark Saltzman, Ph.D., saw a serendipitous opportunity, even if the Goizueta Foundation Professor of Biomedical Engineering and professor of cellular and molecular physiology and of chemical engineering wasn’t sure where it would lead. One of his postdocs had been looking at nanoparticles that would circulate through the blood to target tumors for drug delivery. Instead, he found that the particles stuck to proteins and tissues.

“That is not what we wanted them to do,” Saltzman says. Still, his team thought they might find a use for these sticky nanoparticles. The postdoc, Yang Deng, Ph.D., tested them on skin samples, and found they still stuck fast.

When Asiri Ediriwickrema, M.D. ’14, then a medical student working in Saltzman’s lab, got a look at these bioadhesive nanoparticles (BNPs), he saw clinical possibilities. His first thought was sunscreen.

Saltzman’s team found a way to encase an organic sunscreen agent called padimate O inside the sticky nanoparticles. Padimate O, the active ingredient in many commercial sunscreens, soaks up the sun’s UV rays, but also soaks into the skin. Nanoparticles, on the other hand, are too large to pass through hair follicles and pores, and they remain on the skin’s surface even when it’s wet.

Such a sunscreen could answer the concerns of those who fear that UV-absorbing chemicals have harmful side effects. The next step was to find an expert on photodamage of the skin to see whether the team’s nonabsorbent sunscreen would work. The team knew just the person: Michael Girardi, M.D., professor of dermatology. His lab specializes in the early events of skin cancer development, and in examining the molecular markers of direct and indirect damage from UV exposure. “Yale is a small community,” Saltzman says. “People know what others are doing and you can quickly get to the person you need.”

Saltzman and his team reached out to Girardi, and “there was instant chemistry,” Girardi says. “And a recognition that together we could accomplish so much more than individually.”

The two labs joined forces to test the sunscreen on mouse skin and pigskin models. “We were floored with its performance,” Girardi says. Not only did the sunscreen adhere to skin for up to a full day and absorb UV rays, but it did not penetrate the skin. What’s more, the sunscreen, which used less than 5 percent of the active agent as commercial sunscreen, proved equally effective.

All of this means that the team is on the way to building a longer-lasting and less toxic sunscreen. Chemicals in commercial sunscreen can cause allergies, and have been found in urine and breast milk. While such concerns as hormonal side effects have yet to be proven, “a lot of people feel that if they could avoid having these chemicals get inside the body, they would choose to,” Girardi says. “This technology would give them that choice.”

The team’s findings were recently published in the journal Nature Materials, with Deng and Ediriwickrema as co-first authors. Planning has begun for a clinical trial, and the team has received a pilot grant to explore the new technology further. They’ll be testing its effectiveness with other sunblock agents and addressing additional safety concerns.

Beyond that, Girardi and Saltzman see even greater potential for the sticky nanoparticle: they are looking at how it might be used to treat other skin conditions. “We have come up with more than 100 other possible ways to use it,” says Girardi.