Integration of Phospholipid-Complex Nanocarrier Assembly with Endogenous N-Oleoylethanolamine for Enormously Effective Stroke Therapy

Abstract

Leading to more and more deaths and disabilities, stroke has become a serious threat to human health. What's more, few effective drugs are available in clinic till now. In this research, we prepared a novel neuroprotective nanoformation (OEA-SPC NPs) via the combination of the nanoparticle drug delivery system with the endogenous N-oleoylethanolamine (OEA). By forming hydrogen bond between OEA and the carrier - soybean phosphatidylcholine (SPC), the form of OEA was turned into amorphus state when loading to the nanoparticles, which greatly improved its bioavailability. Then the following systematic experiments revealed the amazing neuroprotective effect of OEA-SPC NPs in vivo. Compared with the MCAO group, the cerebral infarct volume was reduced by 81.1%, and the edema degree by 78.4% via the oral administration of OEA-SPC NPs. And the neurological deficit scores illustrated that the MCAO rats treated with OEA-SPC NPs exhibited significantly less neurological dysfunction. The Morris water maze test indicated that the spatial learning and memory of cerebral ischemia model rats were almost recovered to the normal level. Besides, the OEA-SPC NPs could inhibit the inflammation of reperfusion to a very slight level. These results suggest that the OEA-SPC NPs have a great chance to be a potential anti-stroke formation for clinic application and actually bring hope to thousands of stroke patients. Funding Statements: This project was supported by the National Natural Science Foundation of China (Nos. 81373407 and 81402921), the Health Science Research Personnel Training Program of Fujian Province (2018-CXB-30), the Fundamental Research Funds for the Central Universities (No. 20720180042), the Natural Science Foundation of Fujian, China (No. 2016D018) and the China Postdoctoral Science Foundation (No. 2017M622080 and 2018M632584). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The experimental protocols were approved by the Animal Care and Use Committee of Medical College of Xiamen University in compliance with the NIH Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23).