Sprayable drug delivery system for psoriasis uses “Trojan horse” style nanoparticles

Researchers at the University of Massachusetts Amherst have invented a new, sprayable psoriasis drug delivery system that can be easily and locally applied to psoriasis lesions. Her work, published in Nature communicationhas the potential to reduce healthcare costs.

Psoriasis is an overreaction of the immune system that results in inflamed or scaly patches on the skin. It also carries the risk of developing psoriatic arthritis, heart disease and mental health problems. This chronic inflammatory disease affects 2-3% of the world's population, or 125 million people. In the United States alone, that number is approximately 8 million, with associated annual healthcare costs estimated at $135 billion.

“The problem is that the treatments are very expensive,” says Ashish Kulkarni, an associate professor of chemical engineering at UMass Amherst and senior author of the paper. “They can also have many side effects. And even if they spend that much money, up to 30 to 40% of patients don’t get a sustained response, so it’s not like it works for everyone.”

Considering cost and ease of use, Kulkarni and his team decided to develop a sprayable treatment. Their previous work found that some nanoparticles can be pro-inflammatory, which is counterproductive in psoriasis.

However, this can be counteracted by using specific lipid nanoparticles that inhibit the main inflammatory pathway. Kulkarni describes this as a Trojan horse – the target immune cell does not recognize this nanoparticle container as a threat, but inside it are drugs designed to disrupt the overactive immune response.

The shape of the particle also plays a role. Inspired by the effectiveness of non-spherical pathogens in infecting cells, the researchers designed and tested nanoparticles in different shapes: rods, ellipses and spheres.

“We found that nanorods interact with cells in unique ways,” says Kulkarni. “They can be absorbed by the cells much more quickly. We can deliver drugs at much higher concentrations if we use lipid nanorods instead of spherical nanoparticles.” As a result, the nanorods inhibited 3.8 times more inflammation than nanoellipses and 4.5 times more than nanospheres.

The hidden warriors sit in the rod-shaped “Trojan Horse”: a combination of two psoriasis medications. This delivery system was 59 times more effective at inhibiting inflammatory responses than free administration of the drug without the nanoparticle system.

“We then incorporated the lipid nanorod into a polymer scaffold,” Kulkarni continues. “The scaffold has a unique matrix system that can hold the nanorods together in a solution, but once we spray it, the nanorods trickle down to the cells and are then taken up by the cells.”

“We wanted this system to be a sprayable system that is easy to apply, but once applied it forms a gel from which nanorods can then be sustainably released into your skin cells.”

They tested this on mice with induced psoriasis-like lesions and found that the mice treated with the new spray were effective in reducing inflammation levels. Mice that received no treatment had a psoriasis severity score of 10.25, while mice that were sprayed with empty nanorods or nanorods loaded with the two psoriasis drugs saw scores drop to 1.33 and 0.66, respectively.

Kulkarni sees the potential in his research to help people with psoriasis. “That sounds like a very promising approach,” he says. “Our laboratory is working hard to develop therapeutics that will be translational. This is a unique platform. This is an easy to use platform. It’s scalable.” Next, he hopes to begin toxicity and long-term efficacy studies in larger animal models.