Supercritical impregnation technology was applied to load acrylic intraocular lenses (IOLs) with methotrexate to produce a sustained drug delivery device to mitigate posterior capsule opacification. Drug release kinetics were studied in vitro and used to determine the drug loading. Loaded IOLs and control IOLs treated under the same operating conditions, but without drug, were implanted ex vivo in human donor capsular bags. The typical cell growth was observed and immunofluorescence staining of three common fibrosis markers, fibronectin, F-actin and α-smooth muscle actin was carried out. Transparent IOLs presenting a sustained release of methotrexate for more than 80 days were produced. Drug loading varying between 0.43 to 0.75 ± 0.03 µgdrug.mg-1IOL were obtained when varying the supercritical impregnation pressure (8 and 25 MPa) and duration (30 and 240 min) at 308 K. The use of ethanol (5 mol%) as a co-solvent did not influence the impregnation efficiency and was even unfavorable at certain conditions. Even if the implantation of methotrexate loaded IOLs did not lead to a statistically significant variation in the duration required for a full cell coverage of the posterior capsule in the human capsular bag model, it was shown to reduce fibrosis by inhibiting epithelial-mesenchymal transformation. The innovative application presented has the potential to gain clinical relevance.

中文翻译：

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超临界流体技术用于创新眼科医疗设备的开发：装有药物的人工晶状体，可减轻后囊混浊。

超临界浸渍技术被应用以甲氨蝶呤加载丙烯酸人工晶状体（IOL），以产生持续的药物输送装置，以减轻后囊混浊。在体外研究了药物释放动力学，并将其用于确定载药量。将在相同操作条件下但无药物处理的负载IOL和对照IOL离体植入人供体囊袋中。观察到典型的细胞生长，并对三种常见的纤维化标记物纤连蛋白，F-肌动蛋白和α-平滑肌肌动蛋白进行了免疫荧光染色。透明的IOL表现出甲氨蝶呤持续释放超过80天。药物载量在0.43至0.75±0.03 µg药物之间变化。当在308 K下改变超临界浸渍压力（8和25 MPa）和持续时间（30和240分钟）时，得到的mg-1IOL。使用乙醇（5 mol％）作为助溶剂不会影响浸渍效率和在某些情况下甚至是不利的。即使在人囊袋模型中植入甲氨蝶呤的IOL并没有导致后囊的完整细胞覆盖所需的持续时间有统计学上的显着变化，也显示出通过抑制上皮-间质转化来减少纤维化。提出的创新应用程序有可能获得临床相关性。即使在人囊袋模型中植入甲氨蝶呤的IOL并没有导致后囊的完整细胞覆盖所需的持续时间有统计学上的显着变化，也显示出通过抑制上皮-间质转化来减少纤维化。提出的创新应用有可能获得临床相关性。即使在人囊袋模型中植入甲氨蝶呤的IOL并没有导致后囊的完整细胞覆盖所需的持续时间有统计学上的显着变化，也显示出通过抑制上皮-间质转化来减少纤维化。提出的创新应用程序有可能获得临床相关性。