Despite all the research aiming to treat ocular diseases, age-related macular degeneration (AMD) remains one of the serious diseases worldwide, which needs to be treated. Neovascularization is a key factor in AMD and thus antiangiogenic therapy is beneficial in reducing the development of new abnormal blood vessels. Axitinib, multireceptor tyrosine kinase inhibitor, is a small molecule that works by blocking vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR) responsible for developing neovascularization. The goal of this study is to develop a sustained release formulation of axitinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles to minimize frequent administration of the drug by intravitreal injection. The nanoparticles were characterized for particle size and zeta potential, as well as using differential scanning calorimetry, transmission electrode microscope, and in vitro drug release profile. The cytotoxicity of the formulation was evaluated on human retinal pigmented epithelium ARPE19 cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt] assay. The cellular uptake, antimigration assay, and vascular endothelial growth factor (VEGF) expression levels were found out in vitro using cells. The optimized formulation was 131.33 ± 31.20 nm in size with -4.63 ± 0.76 mV zeta potential. Entrapment efficiency was found to be 87.9% ± 2.7%. The cytotoxicity of ARPE19 cells was <12% for nanoparticles suggesting the in vitro compatibility at 10 μM concentration of drug. Cellular uptake, antimigration assay, and VEGF expression levels for the nanoparticles suggested greater uptake, significant antiangiogenic potential, and inhibition of VEGF activity. The results showed successful development of axitinib-loaded PLGA nanoparticles as an alternative potential treatment for AMD.

中文翻译：

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用于年龄相关性黄斑变性的载有阿昔替尼的聚（乳酸-乙醇酸共聚物）纳米颗粒：配方开发和体外表征。

尽管进行了旨在治疗眼疾病的所有研究，但与年龄相关的黄斑变性（AMD）仍然是全世界需要治疗的严重疾病之一。新血管形成是AMD的关键因素，因此抗血管生成治疗有利于减少新的异常血管的形成。阿昔替尼是一种多受体酪氨酸激酶抑制剂，是一种小分子，可通过阻断负责发展新血管的血管内皮生长因子受体（VEGFR）和血小板衍生生长因子受体（PDGFR）起作用。这项研究的目的是开发一种载有阿昔替尼的聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒的缓释制剂，以最大程度地减少玻璃体内注射药物的频繁给药。表征了纳米粒子的粒径和Zeta电位，以及使用差示扫描量热法，透射电镜和体外药物释放曲线。通过MTT [3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四溴化铵盐]测定法评价制剂对人视网膜色素上皮ARPE19细胞的细胞毒性。使用细胞在体外发现细胞摄取，抗迁移测定和血管内皮生长因子（VEGF）表达水平。优化的配方尺寸为131.33±31.20 nm，Zeta电位为-4.63±0.76 mV。发现包封率是87.9％±2.7％。对于纳米颗粒，ARPE19细胞的细胞毒性<12％，表明在10μM药物浓度下具有体外相容性。纳米颗粒的细胞摄取，抗迁移测定和VEGF表达水平表明摄取量更大，显着的抗血管生成潜力，并抑制VEGF活性。结果表明，载有阿昔替尼的PLGA纳米颗粒已成功开发，可以替代AMD。