Diabetes treatments have evolved to include transplantation of healthy pancreatic islet cells for individuals with type 1 diabetes and for some, successful transplantation may translate into no longer needing insulin injections. Researchers have been trying to overcome a significant hurdle in ensuring successful transplantation by preventing immunologic rejection of the transplanted cells. Research published in the journal Nature Nanotechnology highlights a new discovery to enhance immunomodulation using rapamycin "nanocarriers" instead of the standard oral medication Rapamune (rapamycin/sirolimus), which is limited by its significant fecal elimination and poor bioavailability—among other notable undesirable side effects.

The research team, led by Professor Evan Scott, associate professor of biomedical engineering at Northwestern McCormick School of Engineering and microbiology-immunology at Northwestern University Feinberg School of Medicine, and colleagues embarked on a journey to optimize the current pancreatic islet cell transplantation. This procedure has been recognized as a potential cure for type 1 diabetes by enhancing the effectiveness of posttransplant immunomodulation. The team has devised a method of isolating rapamycin using nanocarriers—a material used to transport another substance and that promotes targeted exposure to specific cells while sparing other tissues of the immunosuppressant effects of the drug.

Describing their hypothesis, which was tested in a study on mice, Dr. Scott stated, "To avoid the broad effects of rapamycin during treatment, the drug is typically given at low dosages and via specific routes of administration, mainly orally." He added further, "But in the case of a transplant, you have to give enough rapamycin to systemically suppress T cells, which can have significant side effects like hair loss, mouth sores and an overall weakened immune system."

Their findings indicate that SC administered rapamycin-loaded polymersomes avoids fecal elimination and allows for "sustained delivery of rapamycin to immune cell rich organs, especially the axillary lymph nodes," according to the authors.

Dr. Scott stated, "We wondered, can rapamycin be re-engineered to avoid non-specific suppression of T cells and instead stimulate a tolerogenic pathway by delivering the drug to different types of immune cells?" He added further, "By changing the cell types that are targeted, we actually changed the way that immunosuppression was achieved."

The first author on the study, Jacqueline Burke, a National Science Foundation graduate research fellow and researcher working with Dr. Scott, stated that she "could hardly believe her readings when she saw the mice's blood sugar plummet from highly diabetic levels to an even number." She reportedly kept double-checking to make sure it "wasn't a fluke," but saw the number sustained over the course of months.

Ms. Burke was herself diagnosed with type 1 diabetes when she was age 9 years. "At my past program, I worked on wound healing for diabetic foot ulcers, which are a complication of type 1 diabetes," she stated. "As someone who's 26, I never really want to get there, so I felt like a better strategy would be to focus on how we can treat diabetes now in a more succinct way that mimics the natural occurrences of the pancreas in a non-diabetic person."

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