Single synchronous delivery of FK506-loaded polymeric microspheres with pancreatic islets for the successful treatment of streptozocin-induced diabetes in mice.

Immune rejection after transplantation is common, which leads to prompt failure of the graft. Therefore, to prolong the survival time of the graft, immunosuppressive therapy is the norm. Here, we report a robust immune protection protocol using FK506-loaded microspheres (FK506) in injectable hydrogel. Pancreatic islets were codelivered with the FK506 into the subcutaneous space of streptozocin-induced diabetic mice. The islets codelivered with 10 mg/kg FK506 maintained normal blood glucose levels during the study period (survival rate: 60%). However, transplantation of islets and FK506 at different sites hardly controlled the blood glucose level (survival rate: 20%). Immunohistochemical analysis revealed an intact morphology of the islets transplanted with FK506. In addition, minimal number of immune cells invaded inside the gel of the islet-FK506 group. The single injection of FK506 into the local microenvironment effectively inhibited immune rejection and prolonged the survival time of transplanted islets in a xenograft model.