Reduction of maturation phenomenon in cerebral ischemia with CDP-choline-loaded liposomes

Purpose. Cerebral ischemia represents a serious therapeutic challenge. We investigated the therapeutic efficacy of CDP-choline-loaded liposomes against cerebral ischemia. The determination of post-ischemic brain recovery by EEG analysis was carried out to evaluate the effect of CDP-choline-loaded liposomes with respect to the free drug on the maturation of ischemic injury. Methods. Long-circulating unilamellar liposomes were prepared by a freeze and thaw procedure followed by an extrusion through polycarbonate membranes. Wistar rats were ischemized by bilateral clamping of the common carotid arteries. Free or liposomally entrapped drug was administered (20 mg/kg) just after ischemia and thereafter once a day for six days. Post-ischemic survival, neuronal membrane peroxidation and brain recovery (EEG analysis) were evaluated. Results. The post-ischemic reperfused rats treated with CDP- choline-loaded liposomes showed a higher survival rate than animals treated with the free drug. The delayed cerebral neurodegenerative injury due to an ischemic event, referred to as maturation phenomenon, was substantially reduced with the administration of the liposomal formulation. The liposomal carrier showed a marked protection against lipoperoxidative damage. Conclusions. Liposomes ensured a rapid recovery of the damaged membranous structure of the neuronal cells, allowing a significant improvement of brain functionality. The reduction of the maturation phenomenon may probably be of particular importance in humans, where a fundamental problem is the quality of life after an ischemic event.