...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biomaterials >Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.
【24h】

Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

机译：基于树状聚合物的靶向玻璃体内治疗，可在视网膜变性中持续减轻神经炎症。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 mug of FA conjugated to 7 mug of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation.
机译：活化的小胶质细胞介导的视网膜神经炎症在年龄相关性黄斑变性和色素性视网膜炎中，在感光细胞和视网膜色素上皮细胞丧失的发病机理中起关键作用。使用羟基封端的聚酰胺酰胺（PAMAM）树状体-药物共轭纳米器件探索了针对视网膜神经炎减轻的靶向药物治疗。我们显示，玻璃体内给药后，PAMAM树状大分子在视网膜变性的两个大鼠模型中选择性地定位在活化的外部视网膜小胶质细胞内，但不在健康对照的视网膜中。通过将氟轻松将丙酮酸与树状聚合物共价结合，可以利用这种依赖病理学的生物分布来进行药物递送。缀合物在90天内持续释放药物。当发生峰值视网膜变性时，使用皇家外科医学院（RCS）大鼠视网膜变性模型在四个星期的时间内评估了体内功效。玻璃化体内注射1杯FA并结合到7杯树状聚合物中，能够阻止视网膜变性，保留感光细胞的外核细胞计数，并减弱整个小胶质细胞。这些研究表明，PAMAM树状聚合物（无靶向配体）具有选择性定位于活化的小胶质细胞的固有能力，并且可以在这些细胞内持续递送药物以治疗视网膜神经炎。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号