title: In vitro and in vivo release characteristics of Tacrolimus (FK506) from an episcleral drug-delivery implant.
abstract: OBJECTIVE
  To investigate the in vitro and in vivo release characteristics of Tacrolimus (FK506) from an episcleral drug-delivery implant.
  
  
  METHODS
  For in vitro experiments, Tacrolimus-loaded implants (0.5 mL; at concentrations of 0.25, 0.5, and 1.0 mg/mL) were immersed in a balanced salt solution. Samples of the surrounding liquid were aspirated at different times over a 96-h period. For in vivo experiments, the experimental group received an implant loaded with Tacrolimus (0.5 mg/mL; 0.5 mL); the control group was given a subconjunctival injection of 0.5 mL Tacrolimus (0.5 mg/mL). On postoperative days 3, 7, 14, 28, and 56, 3 animals were sacrificed, and their eyes were enucleated. Tacrolimus concentrations were determined by liquid chromatographic-tandem mass spectrometry. Ocular toxicity was evaluated by slit-lamp photography, fundus photography, intraocular pressure (IOP), and histology.
  
  
  RESULTS
  The implants released Tacrolimus in a biphasic pattern for 96 h in the in vitro study. The release kinetics were not dependent on the drug concentrations. The in vivo study showed statistically significant differences between the 2 treatment groups. Tacrolimus levels were particularly high in the conjunctiva, iris, ciliary body, cornea, sclera, choroid, and retina in the experimental group, while concentrations were low and only lasted for 1 week in the controls. Slit-lamp photography, fundus photography, IOP, and histology showed no evidence of toxic effects.
  
  
  CONCLUSIONS
  The episcleral drug-delivery implant mechanically released Tacrolimus through the apertures of capsules and, consequently, may be a promising drug vehicle for the treatment of immune-mediated ocular disorders.
authors.affiliation: 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou, China .
authors.forename: Shuyi
authors.initials: S
authors.lastname: Mai
authors.forename: Leilei
authors.initials: L
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Deng
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.forename: Yao
authors.initials: Y
authors.lastname: Zong
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.forename: Qianying
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D065546:Drug Liberation; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D007429:Intraocular Pressure / Q000187:drug effects; D015394:Molecular Structure; D011817:Rabbits; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D007166:Immunosuppressive Agents; D016559:Tacrolimus