title: FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival.
abstract: OBJECTIVE
  FK506 has been extensively used in preventing immune rejection for human organ transplantation. This study aimed to evaluate the effects of a biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber for the prolongation of corneal allograft survival in high-risk keratoplasty.
  
  
  METHODS
  Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506-PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty rabbits. The graft survival time and clinical features of the FK506-PGLC DDS group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and 0.5% FK506 drops groups. The histopathological examination was performed to evaluate the safety of the FK506-PGLC DDS.
  
  
  RESULTS
  The mean graft survival time was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506 concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a sustained release for at least 168 days. No adverse reactions were observed in the FK506-PGLC DDS group.
  
  
  CONCLUSIONS
  Biodegradable FK506-PGLC DDS implanted into anterior chamber can effectively prevent immune rejection in high-risk keratoplasty model, presenting a promising approach for the prolongation of corneal allograft survival.
authors.affiliation: Shandong Eye Institute, Qingdao, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Shi
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Lixin
authors.initials: L
authors.lastname: Xie
authors.forename: Shenguo
authors.initials: S
authors.lastname: Wang
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002208:Caproates; D003315:Cornea / Q000473:pathology; D016039:Corneal Transplantation / Q000276:immunology*; D016503:Drug Delivery Systems; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D007783:Lactones; D009994:Osmolar Concentration; D011091:Polyesters; D011108:Polymers; D011817:Rabbits; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D002208:Caproates; D007783:Lactones; D011091:Polyesters; D011108:Polymers; C507868:poly(glycolide-co-lactide-co-caprolactone); C121056:caprolactone; D016559:Tacrolimus