Integration of phospholipid-complex nanocarrier assembly with endogenous N-oleoylethanolamine for efficient stroke therapy

Abstract

BackgroundLeading 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.ResultsIn 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 efficient 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (10.1186/s12951-019-0442-x) contains supplementary material, which is available to authorized users.

Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model

“…OEA Biodistribution In Vivo. As we previously described (Yang et al, 2019), OEA at dose of 30 or 60 mg/kg was injected into peritoneal cavity of C57BL/6 mice. At 1, 5, 10, 20, 30, 60, 120, 240, and 360 minutes postinjection, the mice were sacrificed, and the liver was excised, which was followed by a washing of the surface with 0.9% NaCl for fluorescence intensity measurement (Cambridge Research & Instrumentation).…”

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke

“…The MWM task was performed from day 15 to day 20 after MCAO [ 19 ]. It was performed in a circular pool (diameter of 150 cm and height of 50 cm) filled with water (20–22°C, 30 cm in depth) and divided into four equal quadrants (quadrants I, II, III, and IV).…”

Endocannabinoidome and its role in neurological disorders-A comprehensive update of existing literature

“…Reduction in infarct volume and cerebral edema was also observed. OEA-SPC NPs was also shown to inhibit the in lammation of reperfusion to a very slight level [117].…”