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Sodium hyaluronate gels as a drug‐release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery
Author(s) -
Spitzer Martin S.,
Yoeruek Efdal,
Kaczmarek Radoslaw T.,
Sierra Ana,
Aisenbrey Sabine,
Grisanti Salvatore,
BartzSchmidt Karl U.,
Szurman Peter
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2007.01149.x
Subject(s) - sodium hyaluronate , cytotoxicity , chemistry , balanced salt solution , dexamethasone , hyaluronic acid , pharmacology , biocompatibility , sodium , in vitro , biochemistry , chromatography , medicine , endocrinology , anatomy , organic chemistry
. 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 m m ). 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.