Endogenous N-oleoylethanolamine Crystals loaded Liposomes with Enhanced Hydrophobic Drug Loading Capacity for Efficient Stroke Therapy

Abstract Background. Although the preparation of liposomes achieves great success and many have received regulatory approval, their retention of highly hydrophobic drugs is still problematic. Results. Herein we report a novel strategy for efficiently loading hydrophobic drug to liposomes for stroke therapy. N-oleoylethanolamine (OEA), an endogenous highly hydrophobic molecule with outstanding neuroprotective effect, was successfully loaded to OEA-SPC&DSPE-PEG liposomes (OSDP LNPs) with a drug loading of 15.9 ± 1.2 wt%, four times higher than those prepared via traditional methods. Efficient retention in OSDP LNPs greatly improved the pharmaceutical property and therefore enhanced the neuroprotective effect of OEA. Through the data of positron emission tomography (PET) and TTC-stained brain slices, it could be clearly visualized that the acute ischemic brain tissues were preserved as penumbral tissues and bounced back with reperfusion. The in vivo experiments stated that OSDP LNPs could significantly improve the survival rate, the behavioral score, the spatial learning and memory ability of the MCAO (middle cerebral artery occlusion) rats. Meanwhile, the cerebral infarct volume, the edema degree, the apoptosis of the neurons and the inflammation within the brain were also greatly decreased. Conclusions. These results suggest that the OSDP LNPs have a great chance to develop hydrophobic OEA into a potential anti-stroke formulation.