FK506 and Rapamycin Bioconjugation: A Proposal to Increase the Viability of Transplanted Pancreatic Islets

Type 1 Diabetes Mellitus is a widespread disease stemming from the improper functioning of pancreatic islets’ ß-cells which produce insulin, a sugar regulatory hormone. There is currently no cure. If the patient has received an islet transplant, damaging blood-mediated inflammatory responses (IBMIR) can ensue, and in addition frequent dosages of immunosuppressants that ultimately can cause chronic health issues are required. Even with immunosuppression therapy, IBMIR and other immune responses result in the destruction of many of the transplanted islets. Attempts to remediate these problems have been made in the form of surface modifications of the transplanted islets. The following thesis proposes a new method to increase the viability of transplanted pancreatic islets-- modification via esterification of the immunosuppressant drugs, specifically FK506 and Rapamycin, for immobilization followed by slow release by a ß-eliminative linker which results in an introduction of the uninhibited version of the immunosuppressant molecule into a localized area.