Cyclosporine A‐loaded and limbal stem cell‐seeded nanofibers for the local suppression of inflammatory and transplantation reactions

Abstract

AbstractPurpose Purpose. To prepare nanofibers containing the immunosuppressive drug cyclosporine A (CsA) and to assess the potential of these nanofibers to inhibit allotransplantation and inflammatory reactions in vitro and in vivo.Methods Methods. Nanofibers containing 10 weight percent of CsA were prepared from biocompatible polymer poly(L‐lactid) by electrospinning procedure. The kinetics of drug release was characterized in aqueous solutions in vitro and in vivo. The growth of mouse limbal stem cells (LSC) on CsA‐loaded nanofibers was evaluated. The ability of CsA‐loaded nanofibers to inhibit allotransplantion reactions in vitro and inflammatory reactions in vivo was characterized.Results Results. The incorporation of CsA into PLA polymer did not influence the pharmacological activity of CsA nor affected the diameter, shape or architecture of nanofibers. The addition of CsA‐containing nanofibers into mixed lymphocyte culture significantly inhibited in a dose‐dependent manner cell proliferation and production of proinflammatory cytokines IL‐2, IL‐17 and IFN‐ Mouse LSC grew on CsA‐loaded nanofibers comparably as on CsA‐free nanofibers. The covering of inflammatory sites with CsA‐loaded nanofibers significantly attenuated the local inflammatory reaction.Conclusion Conclusion. The CsA‐loaded and LSC‐seeded electrospun nanofibers can be used as scaffolds for LSC transfer and simultaneously as drug carriers for the local suppression of transplantation and inflammatory reactions.