title: The distribution, release kinetics, and biocompatibility of triamcinolone injected and dispersed in silicone oil.
abstract: OBJECTIVE
  Triamcinolone acetonide (TA) has been proposed as an adjuvant to pars plana vitrectomy with silicone oil for the surgical treatment of proliferative vitreoretinopathy and proliferative diabetic retinopathy. However, to date no data about the distribution and pharmacokinetics of lipophilic TA injected into silicone oil have been reported.
  
  
  METHODS
  An artificial vitreous space chamber was filled with silicone oil. TA was either injected or dispersed into silicone oil. TA release using a continuous flow model was measured spectrophotometrically. To determine the antiproliferative or cytotoxic effect of the released TA, monolayer cultures of retinal pigment epithelial cells (ARPE19) and retinal ganglion cells (RGC5) were used. Bromodeoxyuridine incorporation, MTT assay, and scanning electron microscopy were performed.
  
  
  RESULTS
  Injected TA sank slowly through the silicone oil and started to sediment below the silicone oil bubble shortly after injection. After the simulated intravitreal injection, no TA could be retrieved from the silicone oil bubble. In contrast, when a suspension of silicone oil and TA was prepared before injection, stable noncytotoxic amounts of TA (25 microg/mL) could be retrieved for up to 90 days. After mere injection (without previous suspension in silicone oil), the sedimented TA crystals showed a pronounced cytotoxic effect.
  
  
  CONCLUSIONS
  Intravitreally injected TA does not mix with silicone oil. TA crystals that sediment at the lower border of a silicone oil bubble may be harmful to retinal cells. A suspension of TA in silicone oil may exhibit safer extended release over several days.
authors.affiliation: Tübingen University Eye Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Spitzer
authors.forename: Radoslaw T
authors.initials: RT
authors.lastname: Kaczmarek
authors.forename: Efdal
authors.initials: E
authors.lastname: Yoeruek
authors.forename: Katrin
authors.initials: K
authors.lastname: Petermeier
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.forename: Hanno
authors.initials: H
authors.lastname: Heimann
authors.forename: Gesine B
authors.initials: GB
authors.lastname: Jaissle
authors.forename: Karl U
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000378:metabolism*; D005938:Glucocorticoids / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D007267:Injections; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000648:ultrastructure; D012827:Silicone Oils / Q000378:metabolism*; D014018:Tissue Distribution; D014222:Triamcinolone Acetonide / Q000493:pharmacokinetics* / Q000633:toxicity; D014822:Vitreous Body
chemical_list: D005938:Glucocorticoids; D012827:Silicone Oils; D014222:Triamcinolone Acetonide