title: In vitro sustained human transscleral drug delivery of fluorescein-labeled dexamethasone and methotrexate with fibrin sealant.
abstract: OBJECTIVE
  To study the use of fibrin sealant as a drug delivery system for the sustained transscleral delivery of dexamethasone and methotrexate.
  
  
  METHODS
  Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber. Dexamethasone-fluorescein or methotrexate-fluorescein in either fibrin sealant or balanced salt solution (BSS) was applied to the episcleral surface. BSS was perfused to the choroidal side, fluorescence was measured in perfusate fractions, and an apparent scleral permeability P(A) was calculated for each solute-vehicle combination.
  
  
  RESULTS
  P(A) for both compounds was significantly lower with fibrin sealant delivery compared to delivery in BSS (p < 0.001). However, the fibrin sealant vehicle provided a more sustained release of both drugs through 24 hr.
  
  
  CONCLUSIONS
  Incorporating dexamethasone and methotrexate into a fibrin sealant provided a more gradual drug delivery and a more uniform delivery compared to dissolving these drugs in BSS. Fibrin sealant could be useful for transscleral delivery for posterior segment disease.
authors.affiliation: Department of Ophthalmology, University Hospital of Maastricht, The Netherlands.
authors.forename: Lars P J
authors.initials: LP
authors.lastname: Cruysberg
authors.forename: Rudy M M A
authors.initials: RM
authors.lastname: Nuijts
authors.forename: Jake A
authors.initials: JA
authors.lastname: Gilbert
authors.forename: Dayle H
authors.initials: DH
authors.lastname: Geroski
authors.forename: Fred
authors.initials: F
authors.lastname: Hendrikse
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
mesh_terms: D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D015718:Fibrin Tissue Adhesive; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D010539:Permeability; D012590:Sclera / Q000378:metabolism*; D014014:Tissue Adhesives
chemical_list: D015718:Fibrin Tissue Adhesive; D005452:Fluoresceins; D005938:Glucocorticoids; D014014:Tissue Adhesives; C103864:fluorescein-methotrexate; D003907:Dexamethasone; D019793:Fluorescein; D008727:Methotrexate