Project 466784

Introduction: Islet transplantation is an effective way that type 1 diabetic patients can be freed from insulin injections, however the lifelong immunosuppression required to subvert the immune response remains a major barrier. Chronic systemic (affecting whole body) immunosuppression often results in multiple toxicities that can reduce the quality of life of transplant recipients. This project explores the use of a localized drug delivery system to preserve transplanted islet function and potentially circumvent the need for systemic immunosuppression.Poly(lactic-co-glycolic acid) is an FDA-approved biomaterial that can form particles that encapsulate and releases drugs. Rapamycin (rapa) is a potent immunosuppressant used in clinical islet transplantation, and its chemical properties makes it an ideal candidate for PLGA particle encapsulation. We hypothesize that this localized rapa-releasing system will subvert the immune response pathways, promoting long-term durable islet function in a transplanted diabetic mouse model under the skin.Methods: Rapa-releasing particles were made and characterized: encapsulation efficiency, structure, and rate of drug release. To examine immune unrelated effects of rapa particles on transplanted islet function, we co-transplanted syngeneic islet (genetically identical recipient and donor). Later, we will use an allogenic diabetic mouse model (non-identical donor and recipient) to determine how well rapa particles can prolonging allograft function. Graft function is monitored through blood glucose levels: non-fasted and fasted following glucose injection.Conclusion: If our hypothesis holds true, rapa particles has the potential to replace chronic systemic immunosuppression and its associated toxicities in islet transplantation.