Spitzer Martin S, Yoeruek Efdal, Kaczmarek Radoslaw T, Sierra Ana, Aisenbrey Sabine, Grisanti Salvatore, Bartz-Schmidt Karl U, Szurman Peter
Department of Ophthalmology, University of Tuebingen, Tuebingen, Germany.
Acta Ophthalmol. 2008 Dec;86(8):842-8. doi: 10.1111/j.1755-3768.2007.01149.x.
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.
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.
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.
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.
评估市售透明质酸钠凝胶中浓缩亲水性类固醇制剂的释放动力学、生物相容性和抗增殖潜力，作为青光眼手术的潜在辅助药物。
将地塞米松与1%透明质酸钠（Healon）和2.3%透明质酸钠（Healon 5）混合，制成地塞米松浓度为4 - 20 mg/ml（7.7 - 38 mmol/L）的透明质酸钠制剂。在2 - 6天内，通过分光光度法测定其在平衡盐溶液（BSS）或磷酸盐缓冲盐水（PBS）中的非累积释放和累积释放。对于细胞毒性试验，将人Tenon成纤维细胞（HTFB）和人视网膜色素上皮细胞（ARPE19）在无血清培养基中培养以确保静态环境；采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）试验和活/死细胞介导的细胞毒性试验来排除细胞毒性。通过将5'-溴-2'-脱氧尿苷（BrdU）掺入细胞DNA来监测细胞增殖活性。
1%和2.3%透明质酸钠的释放动力学几乎相同。在非累积测量中，约44小时后达到稳态。以时间平方根为函数绘制的释放曲线与主要受扩散控制的释放系统一致。未观察到细胞毒性。载有地塞米松的透明质酸钠对HTFB和ARPE19细胞显示出显著的抗增殖作用。
载有地塞米松的透明质酸钠在近2天内显示出类固醇的缓释，其浓度足以抑制HTFB和RPE细胞的增殖而不引起细胞毒性作用。因此，该制剂可能是青光眼手术或其他需要抑制细胞生长的手术中易于制备的辅助药物。
