Nanoparticles may treat autoimmune disease

Lupus and other autoimmune diseases such as Type 1 diabetes may be cured with a novel method of drug delivery.

In a study published March 1 in The Journal of Clinical Investigation, Yale researchers found that delivering lupus drugs directly to specific immune cells using nanoparticles can extend the lifespan of mice infected with lupus. Without nanoparticle delivery, current drugs for lupus are short-lasting and require large doses to be effective, but this mode of delivery would require lower dosages of medication, said senior author Tarek Fahmy, associate professor of biomedical engineering at the Yale School of Engineering & Applied Science

“When you take the drug by itself, the drug molecules are diluted throughout the whole body, so that’s why you have to inject a lot more to get to the target cells,” Fahmy said. “You need a very high dose of the drug, but then there are a lot of side effects that complicate the disease and can make matters worse.”

Though medication deactivates cells causing lupus symptoms by suppressing their response, the drugs may also be toxic to other types of cells that do not cause lupus, he added.

Lead author Michael Look, a Yale postdoctoral associate in biomedical engineering, found that the nanogels — the nanoparticles used to deliver the drugs — could specifically target the cells responsible, thereby achieving the same efficacy as conventional drugs but with much lower doses. The nanogels also remain in the body longer than conventional drugs to provide long-lasting treatment, Look said.

Fahmy said nanoparticles have been used to enhance drug delivery for decades, but recent improvements in nanoparticle technology and a greater understanding of autoimmune diseases have helped him pioneer its application to lupus.

“This technique is more dominant in cancer applications, where it’s used primarily to target tumor cells,” Fahmy said. “But the application to autoimmunity has been limited because of a dearth of understanding of the [molecules] that activate immunity.”

The next step in the research is to compare different lupus drugs delivered by the nanogel and eventually use it in clinical trials, Fahmy said, adding that he hopes the technology will become available in the next four to five years.

Look said that beyond serving as an improvement on conventional drug treatments, nanogels may also offer a permanent cure for lupus by “re-educating the immune system” to avoid attacking its own cells.

For the nanogels to treat other autoimmune diseases, researchers simply need to change the nanogel’s target to the specific cells implicated in that disease — a technique Fahmy said should be “straightforward.” Fahmy said he hopes to test nanogels in Type 1 diabetes treatment with collaborators in the medical school.

“The clinical partnership and basic science is critical for success of this approach,” Fahmy added.

Approximately 1.5 million Americans have lupus, according to the Lupus Foundation of America.

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