Abstract
The present study aims to investigate the neuroprotective effects of carnosine-entrapped elastic liposomes (CAR-ELs) against cerebral ischemia. CAR-ELs were prepared by extrusion method using egg phosphatidylcholine (eggPC) as a phospholipid and Tween 80 (TW80) as an edge activator (eggPC:TW80 = 8:2, w/w). The prepared CAR-ELs were purified by centrifugal ultrafiltration followed by characterization for particle size, polydispersity index, zeta potential and entrapment efficiency. The elasticity of CAR-ELs, the most distinct feature of elastic liposomes, was determined using a stainless steel pressure filter and compared with that of conventional liposomes. In vivo neuroprotective effects of CAR-ELs were evaluated in cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO) in rats. CAR-ELs (250 mg/kg of CAR) were intravenously administered 20 min before pMCAO and 6 h after pMCAO, respectively. The infarct volume in brain was measured by staining with 2,3,5-triphenyltetrazolium chloride after 24 h of cerebral ischemia. CAR-ELs showed nanometric particle size near 100 nm and homogeneous distribution with polydispersity index below 0.1. The elasticity of CAR-ELs was 2-fold higher than that of conventional liposomes. The brain ischemia was successfully developed with pMCAO as indicated by highly infarcted hemisphere (~ 50%) in saline-treated rats. The pre-treatment with CAR-ELs significantly reduced infarct volume (7.9%) compared with CAR solution (19.1%)- and saline (50.8%)-pretreated rats. CAR solution, however, showed better neuroprotective effects than CAR-ELs when administered 6 h after ischemia induction. The pre-treatment with CAR-ELs could be promising nanocarrier-based neuroprotective therapeutics against ischemic stroke.
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