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Development of drug-eluting intraocular lens for improving post-cataract surgical complications

机译:用于改善白内障术后并发症的药物洗脱人工晶状体的开发

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Introduction: Cataract is a serious eye condition affecting millions of people worldwide. Although the implantation of intraocular lens (IOL) can be routinely performed, the post-cataract surgery-related inflammation and posterior capsule opacification are common symptoms. To address these drawbacks, this study aims to develop a novel drug-eluting IOL that can effectively exhibit anti-cell adhesion and anti-inflammatory activities. Materials and Methods: The IOL samples (IOL-C group) were pre-treated with oxygen plasma (IOL-OP group) and modified with hetero-bifunctional poly(ethylene glycol) (PEG) derivatives (IOL-PEG group). After conjugation with matrix metalloproteinase (MMP)-sensitive peptide, the IOLs were further loaded with the drug amfenac (IOL-AF) by carbodiimide coupling reaction. Surface characterizations and biocompatibility assessments were performed. Then, the protein adsorbed amount, cell adhesion ratio, and drug release profile were also determined. In a rabbit model of experimental cataract, the therapeutic efficacy of drug-eluting IOL was evaluated. All animal procedures were approved by the Institutional Review Board and were carried out in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Results and Discussion: FTIR, ESCA, AFM, and water contact angle studies indicated that surface modification of functionalized IOLs can be successfully achieved. Light transmittance measurements demonstrated that the surface functionalization with PEG does not alter the optical properties of IOL materials. In vitro and in vivo studies showed that the functionalized IOLs are biocompatible towards lens epithelial cell cultures and anterior segment tissues. However, changes in anti-protein adsorption and anti-cell adhesion appear to be significant on IOL-PEG, suggesting crucial role of PEG molecules on the IOL surfaces. Our results show a programmable release of drug from the samples of IOL-AF groups. In addition, studies on degree of oxidative stress and inflammation level indicate a significant decrease in the generation of ROS, intracellular calcium level, COX-2 activity, and PGE2 level in IOL-AF groups. Results of animal tests further confirmed the pharmacological action of the amfenac released from the functionalized IOLs. Slit-lamp examinations, IOP measurements, and immunohistochemistry demonstrate the limited inflammation after 28 days of surgical insertion of drug-eluting IOL implants. Conclusion: The present study suggests that the drug-eluting IOLs are more effective and beneficial than traditional postoperative treatments with the possibility to last for up to 28 days. The biomaterial-functionalized IOLs may hold promise to address common post-cataract surgical complications.
机译:简介:白内障是一种严重的眼部疾病,影响了全球数百万人。尽管可以常规进行人工晶状体(IOL)的植入,但白内障手术后相关的炎症和后囊混浊是常见的症状。为了解决这些缺点,本研究旨在开发一种新型的药物洗脱IOL,该IOL可有效显示抗细胞粘附和抗炎活性。材料和方法:将IOL样品(IOL-C组)用氧等离子体预处理(IOL-OP组),并用杂双功能聚乙二醇(PEG)衍生物(IOL-PEG组)进行修饰。与基质金属蛋白酶(MMP)敏感肽缀合后,通过碳二亚胺偶联反应向IOL进一步加载药物安非那克(IOL-AF)。进行了表面表征和生物相容性评估。然后,还测定了蛋白质的吸附量,细胞粘附率和药物释放曲线。在实验性白内障的兔子模型中,评估了药物洗脱IOL的治疗效果。所有动物程序均已获得机构审查委员会的批准,并按照《 ARVO眼科和视觉研究中使用动物的声明》进行。结果与讨论:FTIR,ESCA,AFM和水接触角研究表明,可以成功实现功能化IOL的表面改性。透光率测量表明,PEG的表面功能化不会改变IOL材料的光学特性。体外和体内研究表明,功能化的IOL对晶状体上皮细胞培养物和前节组织具有生物相容性。但是,抗蛋白质吸附和抗细胞粘附的变化在IOL-PEG上似乎很重要,表明PEG分子在IOL表面上起着至关重要的作用。我们的结果表明,可从IOL-AF组的样品中以可编程方式释放药物。此外,对氧化应激程度和炎症水平的研究表明,IOL-AF组的ROS生成,细胞内钙水平,COX-2活性和PGE2水平显着降低。动物试验结果进一步证实了从功能化IOL中释放出的安非那克的药理作用。裂隙灯检查,IOP测量和免疫组化显示,在外科手术插入药物洗脱IOL植入物28天后,炎症有限。结论:本研究表明药物洗脱的人工晶体比传统的术后治疗更有效和有益,并且可能持续长达28天。生物材料功能化的人工晶体可能有望解决白内障术后常见的并发症。

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