title: Cyclosporine A Loaded Electrospun Poly(D,L-Lactic Acid)/Poly(Ethylene Glycol) Nanofibers: Drug Carriers Utilizable in Local Immunosuppression.
abstract: OBJECTIVE
  The present study aims to prepare poly(D,L-lactic acid) (PLA) nanofibers loaded by the immunosuppressant cyclosporine A (CsA, 10 wt%). Amphiphilic poly(ethylene glycol)s (PEG) additives were used to modify the hydrophobic drug release kinetics.
  
  
  METHODS
  Four types of CsA-loaded PLA nanofibrous carriers varying in the presence and molecular weight (MW) of PEG (6, 20 and 35 kDa) were prepared by needleless electrospinning. The samples were extracted for 144 h in phosphate buffer saline or tissue culture medium. A newly developed and validated LC-MS/MS method was utilized to quantify the amount of released CsA from the carriers. In vitro cell experiments were used to evaluate biological activity.
  
  
  RESULTS
  Nanofibers containing 15 wt% of PEG showed improved drug release characteristics; significantly higher release rates were achieved in initial part of experiment (24 h). The highest released doses of CsA were obtained from the nanofibers with PEG of the lowest MW (6 kDa). In vitro experiments on ConA-stimulated spleen cells revealed the biological activity of the released CsA for the whole study period of 144 h and nanofibers containing PEG with the lowest MW exhibited the highest impact (inhibition).
  
  
  CONCLUSIONS
  The addition of PEG of a particular MW enables to control CsA release from PLA nanofibrous carriers. The biological activity of CsA-loaded PLA nanofibers with PEG persists even after 144 h of previous extraction. Prepared materials are promising for local immunosuppression in various medical applications.
authors.affiliation: Department of Polymer Networks and Gels, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06, Prague 6, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Sirc
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hampejsova
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Trnovska
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kozlik
authors.affiliation: Department of Polymer Networks and Gels, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06, Prague 6, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Hrib
authors.affiliation: Department of Polymer Networks and Gels, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06, Prague 6, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Hobzova
authors.affiliation: Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
authors.affiliation: Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic. bosakova@natur.cuni.cz.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Bosakova
mesh_terms: D002460:Cell Line; D003470:Culture Media; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D065546:Drug Liberation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D057139:Nanofibers / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000166:cytology; D013499:Surface Properties; D046509:Tissue Culture Techniques
chemical_list: D003470:Culture Media; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide); D016572:Cyclosporine
keywords: LC-MS/MS; cyclosporine A; drug release kinetics; poly(D,L-lactic acid) nanofibers; poly(ethylene glycol)