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: glycolipid-like polymer, A-317491, nanostructured lipid carriers, endometriosis pain, P2X₃ receptor