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首页> 美国卫生研究院文献>Drug Delivery >Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein
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Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein

机译：透明质酸修饰的MPEG-b-PAE嵌段共聚物水性胶束用于疏水性染料木黄酮的眼科药物有效递送

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摘要

The ophthalmic drug delivery is a challenge in the clinical treatment of ocular diseases. The traditional drug administration usually shows apparent limitations, such as the low bioavailability from the reason of low penetration of the cornea and the short survival time of drug in the eyes. To overcome these shortcomings, we propose an amphiphilic polymer micelle modified with hyaluronic acid (HA) for high efficient ophthalmic delivery of genistein, a widely used hydrophobic drug for treatment of ocular angiogenesis. The MPEG-b-PAE copolymer was synthesized by the Michael addition reaction, and the final drug carrier MPEG-b-PAE-g-HA was obtained by the process of esterification. Then, genistein was packaged in this drug carrier, getting the final micelles with size of about 84.5 nm. The cell viability tests showed that the micelles take no obvious cytotoxicity to the human cornea epithelium cells. The functionalities of drug slow release and cornea penetration ability were demonstrated in a series ex vivo experiments. Further, the vascular inhibition test illustrated that the micelles could significantly inhibit the angiogenesis of human umbilical vein endothelial cells. These results indicate that the constructed polymer has high feasibility to be used as drug carrier in the treatment of ocular diseases.
机译：眼科药物递送是眼科疾病的临床治疗中的挑战。传统药物的给药通常表现出明显的局限性，例如由于角膜渗透率低和眼内药物存活时间短的原因，导致生物利用度低。为了克服这些缺点，我们提出用透明质酸（HA）修饰的两亲性聚合物胶束，用于染料木黄酮的眼部高效递送，染料木黄酮是一种广泛使用的疏水性药物，用于治疗眼部血管新生。通过迈克尔加成反应合成了MPEG-b-PAE共聚物，并通过酯化过程获得了最终的药物载体MPEG-b-PAE-g-HA。然后，将染料木黄酮包装在这种药物载体中，得到的最终胶束大小约为84.5 nm。细胞活力测试表明，胶束对人角膜上皮细胞没有明显的细胞毒性。在一系列体外实验中证明了药物缓慢释放和角膜渗透能力的功能。此外，血管抑制试验表明，该胶束可以显着抑制人脐静脉内皮细胞的血管生成。这些结果表明，所构建的聚合物具有高度的可行性，可以用作治疗眼疾病的药物载体。

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