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Abstract #22454 Published in IGR 10-4
Sodium hyaluronate gels as a drug-release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery
Spitzer MS; Yoeruek E; Kaczmarek RT; Sierra A; Aisenbrey S; Grisanti S; Bartz-Schmidt KU; Szurman PActa Ophthalmologica 2008; 86: 842-848
PURPOSE: 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. CONCLUSION: 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.
Dr. M.S. Spitzer, Department of Ophthalmology, University of Tübingen, Tübingen, Germany. Martin.Spitzer@med.uni-tuebingen.de
