UNASSIGNED: PLGA nanoparticles loaded with FK506 were prepared by the solvent evaporation method. The characterization of FK506 NPs was evaluated by electron microscopy. To confirm the function and safety of FK506 NPs, these particles were administrated into rats by intraperitoneal injection. The survival time of the allograft, systemic concentration of FK506, anti-rejection activity, and side-effect of FK506 NPs were evaluated in a Brown Norway (BN)-to-Sprague Dawley (SD) epigastric VCA transplantation model.
UNASSIGNED: Compared with the nontreatment, PLGA control and FK506 groups, the median survival times (MST) of the FK506 NP groups were significantly prolonged. The FK506 NPs could maintain therapeutic drug concentration for 60 days. Moreover, cytokine concentrations, flow cytometry of regulatory T cells (Tregs) and histopathology of allografts revealed significantly prolonged immunosuppression by FK506 NPs. FK506 NPs also ameliorated FK506 nephrotoxicity.
UNASSIGNED: FK506 NPs prolong the survival time of VCAs in a murine model with minimal nephrotoxicity, and provide a potential clinical strategy for ameliorating long-term side effects of immunosuppressive therapy.