Sodium hyaluronate gels as a drug-release system for corticosteroids: Release kinetics and antiproliferative potential for glaucoma surgery

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.