Inflammation-Triggered Drug Delivery System Prevents Transplant Rejection

By C. Rajan, contributing writer

A global team of researchers have just developed a novel drug delivery system that delivers a targeted and controlled dose of medication when triggered by inflammation or other immune responses. The study was published online in Science Translational Medicine on August 13, 2014.

Scientists from Brigham and Women’s Hospital (BWH), the Institute for Stem Cell Biology and Regenerative Medicine in Bangalore, India, and University Hospital of Bern, Switzerland, have developed a new system that delivers immunosuppressant drugs locally when subjected to a 'trigger', through the use of a biomaterial that self-assembles into a hydrogel, a gelatin-like material. The novel system provides a controlled release of the medication, which is delivered only where and when it is needed.

This system is particularly useful for transplant cases, where immediately following a tissue graft transplant, doctors normally give transplant recipients immunosuppressant drugs to prevent their immune systems from rejecting and attacking the new body part. However, this process can suppress the immune system unnecessarily and can make a patient vulnerable to infection, toxicity, and other side effects.

The hydrogel-drug combo, which contains the immunosuppressant drug Tacrolimus, is injected under the skin after transplant surgery. The hydrogel remains inactive until it detects an inflammation or other immune response from the transplant site. When it receives this stimulus, it delivers the immunosuppressant drug within the transplanted graft for months until it is required. The researchers claim that such an inflammation-directed drug release offers judicious use of a locally injected drug that extends the release for months while eliminating systemic toxicity.

“This new approach to delivering immunosuppressant therapy suggests that local delivery of the drug to the grafted tissue has benefits in reducing toxicity, as well as markedly improving therapeutic outcomes, and may lead to a paradigm shift in clinical immunosuppressive therapy in transplant surgery,” said Dr. Jeff Karp, associate professor of medicine at Harvard Medical School, Division of Biomedical Engineering, BWH Department of Medicine, and one of the study's corresponding authors.

The researchers found that in pre-clinical studies, a one-time, local injection of the hydrogel-drug combo prevented graft rejection for more than 100 days, as compared to 35.5 days for recipients receiving only Tacrolimus, and 11 days for recipients without treatment or only receiving hydrogel.

This drug delivery system may also be applied in medical situations outside of transplant surgery. “This safe, controlled release platform approach functions for over three months from a single injection, and that has broad implications,” said Karp. “Nearly every disease has an inflammatory component. Thus we believe the materials we have developed could be used for localized treatment of multiple inflammatory diseases.”

Dr. Vemula, another corresponding author of the study said, “This approach should also improve patient compliance, as it obviates the need for daily medications. Also, we plan to expand this prototype for the treatment of numerous diseases such as psoriasis, arthritis, and cancer.”