title: Cyclosporine A-loaded and stem cell-seeded electrospun nanofibers for cell-based therapy and local immunosuppression.
abstract: Cyclosporine A (CsA), a potent immunosuppressive drug with low water solubility, was dissolved in poly(L-lactic acid) (PLA) solution, and nanofibers were fabricated from this mixture by electrospinning technology. The addition of CsA into the PLA solution and the conditions of the electrospinning process did not influence the structure of the nanofibers nor affect the pharmacological activity of CsA. Study of the CsA release behavior in culture medium showed a release for at least 96 h. After the topical application of CsA-loaded nanofibers on skin allografts in vivo, the release was significantly slower and about 35% of the drug was still retained in the nanofibers on day 8. The addition of CsA-loaded nanofibers into cultures of mouse spleen cells stimulated with Concanavalin A selectively inhibited T cell functions; the activity of stimulated macrophages or the growth of non-T-cell populations was not suppressed in the presence of CsA-loaded nanofibers. The covering of skin allografts with CsA-loaded nanofibers significantly attenuated the local production of the proinflammatory cytokines IL-2, IFN-γ and IL-17. These results suggest that CsA-loaded electrospun nanofibers can serve as effective drug carriers for the local/topical suppression of an inflammatory reaction and simultaneously could be used as scaffolds for cell-based therapy.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic. holan@img.cas.cz
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
authors.forename: Milada
authors.initials: M
authors.lastname: Chudickova
authors.forename: Peter
authors.initials: P
authors.lastname: Trosan
authors.forename: Eliska
authors.initials: E
authors.lastname: Svobodova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krulova
authors.forename: Sarka
authors.initials: S
authors.lastname: Kubinova
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
authors.forename: Jakub
authors.initials: J
authors.lastname: Sirc
authors.forename: Jiri
authors.initials: J
authors.lastname: Michalek
authors.forename: Martina
authors.initials: M
authors.lastname: Juklickova
authors.forename: Marcela
authors.initials: M
authors.lastname: Munzarova
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D016572:Cyclosporine