Enhanced Neuroprotection of Ischemic Stroke Based on Liposomal Drug Delivery System Loading a Novel Uncoupler of Ischemia-induced nNOSPSD- 95

A novel candidate named 5-(3,5-dichloro-2-hydroxybenzylamino)-2- hydroxybenzoic acid (ZL006) can effectively treat focal cerebral ischemic stroke. However, the application potential of ZL006 was compromised by its poor solubility. In this study, ZL006 was loaded effectively into liposomes to improve the solubility and bioavailability. The particle size of ZL006-loaded liposomes (LPs) was about 115.5 nm with acceptable polydispersity index. The in vitro release profiles indicated that ZL006 could keep sustained release from LPs for more than 48 h. The results of pharmacokinetics study proved that the mean residence time of LPs group was 1.5-fold (P < 0.05) higher than that of free ZL006 group. Besides, the results of tissue distribution showed that the accumulation of ZL006 in brain tissue was significantly improved compared with the free ZL006 group at 1 h time after intravenous. Anti- ischemic stroke results showed that LPs could significantly enhance neuroprotection of ischemic stroke on middle cerebral artery occlusion (MCAO) rats model. In conclusion, LPs had been demonstrated to be a promising drug delivery system for ZL006 to treat ischemic stroke. Keywords: Liposomes, pharmacodynamics pharmacokinetics, pre-formulation, stroke, tissue distribution.