Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain.
Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain.
复制标题
糖脂类聚合物胶束递送的 A-317491 对子宫内膜异位症疼痛的影响
DOI：
10.2147/ijn.s146569
复制
发表时间：
2017
影响因子：
8
通讯作者：
Hu F
中科院分区：
文献类型：
--
作者：
Yuan M;Ding S;Meng T;Lu B;Shao S;Zhang X;Yuan H;Hu F
子宫内膜异位症是妇科常见病，临床缺乏有效的治疗方法。目前的治疗方法往往会导致子宫内膜异位症疼痛复发和严重的副作用。P2X3受体是一种三磷酸腺苷(ATP)门控离子通道，可能与子宫内膜异位症疼痛有关。在本研究中，壳寡糖-g-硬脂酸聚合物胶束包裹的纳米脂质载体作为一种新型的给药系统，用于治疗子宫内膜异位症疼痛的选择性P2X3受体拮抗剂A-317491。用CSOSA胶束包覆A-317491负载纳米晶(NLC/A-317491)，形成CSOSA/NLC/A-317491纳米粒子。以高表达P2X3受体的嗜铬细胞瘤PC12细胞为细胞模型，CSOSA/NLC/A-317491可部分阻断三磷酸腺苷诱导的钙内流。在裸鼠和大鼠子宫内膜异位症模型中，静脉注射CSOSA/NLC后，CSOSA/NLC可聚集到子宫内膜异位病变中。在子宫内膜异位症大鼠中，CsoSA/NLC/A-317491可逆转机械痛觉过敏和热痛觉过敏的长期效应，这可能是由于CsoSA/NLC/A-317491在子宫内膜异位症病变中大量分布所致。综上所述，CSOSA/NLC纳米粒A-317491可减轻大鼠子宫内膜异位症疼痛，CSOSA/NLC/A-317491可作为P2X3靶向治疗子宫内膜异位症疼痛的有效治疗策略。
Endometriosis is a common gynecological disease with a lack of effective clinical treatment. Current therapy often results in endometriosis pain recurrence and serious side effects. P2X3 receptor, an adenosine triphosphate (ATP)-gated ion channel, might be implicated in endometriosis pain. In this study, chitosan oligosaccharide-g-stearic acid (CSOSA) polymer micelles-coated nanostructured lipid carriers (NLCs) were developed as a novel delivery system for A-317491, a selective P2X3 receptor antagonist for endometriosis pain therapy. A-317491-loaded NLC (NLC/A-317491) could be coated by CSOSA micelles to form CSOSA/NLC/A-317491 nanoparticles. Pheochromocytoma PC12 cells, which highly expressed P2X3 receptors, were used as a cell model, and the CSOSA/NLC/A-317491 partly blocked the Ca2+ influx induced by ATP stimulation. In nude mouse and rat endometriotic models, CSOSA/NLC could accumulate into endometriotic lesions after vein injection. In endometriotic rats, CSOSA/NLC/A-317491 reversed mechanical and heat hyperalgesia with long-term efficacy, which might be attributed to the massive CSOSA/NLC/A-317491 distribution in the endometriotic lesions. In conclusion, A-317491 delivered by CSOSA/NLC nanoparticles attenuated endometriosis pain in rats, and CSOSA/NLC/A-317491 could be used as an effective treatment strategy for P2X3-targeted therapy in endometriosis pain.