title: The immunosuppressive activity of polymeric micellar formulation of cyclosporine A: in vitro and in vivo studies.
abstract: We have previously developed micelles of methoxy poly(ethylene oxide)-b-poly(ε-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 (Sandimmune®). Our results demonstrate that PM-CsA could exert a potent immunosuppressive effect similar to that of Sandimmune® both in vitro and in vivo. Both formulations inhibited phenotypic maturation of DCs and impaired their allostimulatory capacity. Furthermore, both PM-CsA and Sandimmune® 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 Sandimmune®-treated mice have shown impairment in their proliferative response and IFN-γ production at similar levels. These results highlight the potential of polymeric micelles to serve as efficient vehicles for the delivery of CsA.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Dentistry/Pharmacy Centre, Edmonton, Canada.
authors.forename: Samar
authors.initials: S
authors.lastname: Hamdy
authors.forename: Azita
authors.initials: A
authors.lastname: Haddadi
authors.forename: Anooshirvan
authors.initials: A
authors.lastname: Shayeganpour
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Montazeri Aliabadi
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008823:Micelles; D011091:Polyesters; C458722:polyethylene oxide-polycaprolactone copolymer; D007371:Interferon-gamma; D016572:Cyclosporine