Degradable Devices for Localized Delivery of Immunosupressants to Prevent Transplant Rejection

Statement of Purpose: Advances in surgical techniques and immunology have enabled transplantation of composite tissue allografts (CTAs, e.g., upper extremity, face, genitourinary tissues) to treat complex soft tissue injuries and extremity amputations. However, >85% of transplant recipients develop at least 1 episode of rejection within the first year, and >50% experience multiple such episodes. Systemic distribution of orally or intravenously delivered immunosuppressants increases the likelihood of widespread side effects. In addition, the effectiveness of oral administration is dependent on patient compliance. To address these limitations, we have developed a polymeric local drug delivery system using a biodegradable, bioresorbable tyrosine-derived polycarbonate (TyrPC) [1]. The devices are polymeric thin films loaded with the immunosuppressant tacrolimus (FK506). These devices are designed for implantation at the interface between host and donor tissue during transplant surgery to provide long-term, localized immunosuppression and reduce the incidence of rejection episodes.