title: Sodium hyaluronate gels as a drug-release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery.
abstract: OBJECTIVE
  To evaluate the release kinetics, biocompatibility and antiproliferative potential of a concentrated hydrophilic steroid formulation from commercially available sodium hyaluronate gels as a potential adjunct in glaucoma surgery.
  
  
  METHODS
  Dexamethasone and sodium hyaluronate 1% (Healon) and sodium hyaluronate 2.3% (Healon 5) were mixed to yield sodium hyaluronate formulations containing dexamethasone in concentrations of 4-20 mg/ml (7.7-38 mm). Non-cumulative and cumulative release into balanced salt solution (BSS) or phosphate buffered saline (PBS) was measured spectrophotometrically over 2-6 days. For cytotoxicity assays, human tenon fibroblasts (HTFB) and human retinal pigment epithelium cells (ARPE19) were cultured in a serum-deficient medium to ensure a static milieu; 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay and Live/Dead cell-mediated cytotoxicity assay were used to exclude cytotoxicity. Cellular proliferative activity was monitored by 5'-bromo-2'-deoxyuridine (BrdU)-incorporation into cellular DNA.
  
  
  RESULTS
  The release kinetics from sodium hyaluronate 1% and 2.3% were almost identical. Steady state was achieved after approximately 44 hrs in non-cumulative measurements. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. No cytotoxicity could be observed. Dexamethasone-loaded sodium hyaluronate showed a significant antiproliferative effect on HTFB and ARPE19 cells.
  
  
  CONCLUSIONS
  Dexamethasone-loaded sodium hyaluronate shows extended release of steroid over almost 2 days in concentrations high enough to inhibit the proliferation of HTFB and RPE cells without evoking cytotoxic effects. Thus, this formulation may be an easy-to-prepare adjunct in glaucoma surgery or other procedures in which cellular growth inhibition is desired.
authors.affiliation: Department of Ophthalmology, University of Tuebingen, Tuebingen, Germany. Martin.Spitzer@med.uni-tuebingen.de
authors.forename: Martin S
authors.initials: MS
authors.lastname: Spitzer
authors.forename: Efdal
authors.initials: E
authors.lastname: Yoeruek
authors.forename: Radoslaw T
authors.initials: RT
authors.lastname: Kaczmarek
authors.forename: Ana
authors.initials: A
authors.lastname: Sierra
authors.forename: Sabine
authors.initials: S
authors.lastname: Aisenbrey
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Karl U
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage; D005347:Fibroblasts / Q000166:cytology; D005782:Gels; D005901:Glaucoma / Q000601:surgery; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006820:Hyaluronic Acid; D009994:Osmolar Concentration; D055213:Retinal Pigment Epithelium / Q000166:cytology; D013997:Time Factors; D014221:Triamcinolone / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D003692:Delayed-Action Preparations; D005782:Gels; D005938:Glucocorticoids; D014221:Triamcinolone; D003907:Dexamethasone; D006820:Hyaluronic Acid