title: Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model--a pilot study.
abstract: OBJECTIVE
  To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model.
  
  
  METHODS
  Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination.
  
  
  RESULTS
  The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22.
  
  
  CONCLUSIONS
  The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.
authors.affiliation: Centre of Ophthalmology, University Eye Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Spitzer
authors.forename: Macarena
authors.initials: M
authors.lastname: Sat
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schramm
authors.forename: Sven
authors.initials: S
authors.lastname: Schnichels
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schultheiss
authors.forename: Efdal
authors.initials: E
authors.lastname: Yoeruek
authors.forename: Dimitar
authors.initials: D
authors.lastname: Dzhelebov
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001672:Biocompatible Materials; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D005355:Fibrosis / Q000517:prevention & control; D005901:Glaucoma / Q000601:surgery; D006820:Hyaluronic Acid / Q000528:radiation effects*; D010865:Pilot Projects; D011817:Rabbits; D014130:Trabeculectomy; D014466:Ultraviolet Rays; D055675:Viscosupplements / Q000528:radiation effects*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D055675:Viscosupplements; D062367:ortho-Aminobenzoates; D006820:Hyaluronic Acid; C012293:tranilast