Abstract
We have previously developed micelles of methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone) as vehicles for the solubilization and delivery of cyclosporine A (CsA). These micelles were able to reduce the renal uptake and nephrotoxicity of CsA. The purpose of the current study was to test the efficacy of polymeric micellar formulation of CsA (PM-CsA) in suppressing immune responses by either T cells or dendritic cells (DCs). The performance of PM-CsA was compared to that of the commercially available formulation of CsA (SandimmuneA (R)). Our results demonstrate that PM-CsA could exert a potent immunosuppressive effect similar to that of SandimmuneA (R) both in vitro and in vivo. Both formulations inhibited phenotypic maturation of DCs and impaired their allostimulatory capacity. Furthermore, both PM-CsA and SandimmuneA (R) have shown similar dose-dependent inhibition of in vitro T cell proliferative responses. A similar pattern was observed in the in vivo study, where T cells isolated from both PM-CsA-treated and SandimmuneA (R)-treated mice have shown impairment in their proliferative response and IFN-gamma production at similar levels. These results highlight the potential of polymeric micelles to serve as efficient vehicles for the delivery of CsA.