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Endogenous Oleoylethanolamide Crystals Loaded Lipid Nanoparticles with Enhanced Hydrophobic Drug Loading Capacity for
Shichao Wu1,2,3,4, Di Liao3,4,5, Xi Li3,4,5
1Department of Nuclear Medicine (PET Center), Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
Introduction:
Although the preparation of lipid nanoparticles (LNPs) achieves great success, their retention of highly hydrophobic drugs is still problematic.
Methods:
Herein, we report a novel strategy for efficiently loading hydrophobic drugs to LNPs for stroke therapy. Oleoylethanolamide (OEA), an endogenous highly hydrophobic molecule with outstanding neuroprotective effect, was successfully loaded to OEA-SPC&DSPE-PEG lipid nanoparticles (OSDP LNPs) with a drug loading of 15.9 ± 1.2 wt%. Efficient retention in OSDP LNPs greatly improved the pharmaceutical property and enhanced the neuroprotective effect of OEA.
Results:
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 cerebral infarct volume, the edema degree, the spatial learning and memory ability of the MCAO (middle cerebral artery occlusion) rats.
Discussion:
These results suggest that the OSDP LNPs have a great chance to develop hydrophobic OEA into a potential anti-stroke formulation.
