Immunosuppressive agents are used for the treatment of immune-mediated
myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized
liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal
FK506, an immunosuppressive drug encapsulated within
liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune
myocarditis (EAM) model. We prepared
polyethylene glycol-modified liposomal
FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine
myosin and assessed the tissue distribution of the nano-sized beads and liposomal
FK506 in this model. After liposomal or free
FK506 was administered on days 14 and 17 after immunization, the
cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free
FK506,
FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal
FK506 was administered. The administration of liposomal
FK506 markedly suppressed the expression of
cytokines, such as
interferon-γ and
tumor necrosis factor-α, and reduced
inflammation and
fibrosis in the myocardium on day 21 compared to free
FK506. The administration of liposomal
FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free
FK506. Nano-sized
liposomes may be a promising drug delivery system for targeting myocarditic hearts with
cardioprotective agents.