1. Academic Validation
  2. 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

  • Int J Nanomedicine. 2017 Nov 9;12:8171-8183. doi: 10.2147/IJN.S146569.
Ming Yuan 1 Shaojie Ding 2 Tingting Meng 3 Binbin Lu 3 Shihong Shao 1 Xinmei Zhang 2 Hong Yuan 3 Fuqiang Hu 1 3
Affiliations

Affiliations

  • 1 Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan.
  • 2 Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou.
  • 3 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Abstract

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.

Keywords

A-317491; P2X3 receptor; endometriosis pain; glycolipid-like polymer; nanostructured lipid carriers.

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