dipalmitoylphosphatidylserine and Brain-Ischemia

Unilamellar liposomes made up of DPPC-DPPS-Chol (7:4:7 molar ratio) and ganglioside GM1 8% mol were used to deliver cytidine-5I-diphosphate choline (CDP-choline) to the brain. The liposomal suspension consisted of unilamellar vesicles with a mean size of 50 nm and a very narrow size distribution. The therapeutic effectiveness of CDP-choline-loaded liposomes was investigated by an in vivo model of cerebral ischemia on Wistar rats (320-350 g). The animals were made ischemic to different extents (5, 15 and 30 min) by bilateral clamping of the common carotid arteries. The effect of free and liposomally encapsulated CDP-choline on the survival rate of post-ischemic reperfused rats was evaluated. The liposome formulation was much more active against ischemic injury than the free CDP-choline, ensuring a noticeable improvement of the survival rate with regards to the free drug ranging from 45% to 100% as a function of the duration of the ischemic event.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Brain Ischemia; Carotid Artery, Common; Cholesterol; Constriction; Cytidine Diphosphate Choline; G(M1) Ganglioside; Liposomes; Male; Phosphatidylserines; Rats; Rats, Wistar; Survival Rate

Citicoline is a therapeutic agent widely used in the treatment of brain injury, for example in cerebrovascular disease or traumatic accidents. Unfortunately, the strong polar nature of this drug prevents it crossing the blood-brain barrier. In this paper, the possibility of efficiently trapping citicoline in liposomes to improve its therapeutic effects is reported. The citicoline-encapsulation efficiency, drug leakage and size analysis of various liposome systems were studied. The real therapeutic effectiveness of these citicoline liposome formulations was evaluated by biological assay. The effects of free and liposome encapsulated citicoline on survival rate of ischaemic reperfused male Wistar rats (80-100 g) were investigated. Of the phospholipid mixtures used in citicoline liposome formulation the best in terms of delivery and therapeutic effects was 1,2-dipalmitoyl-sn-glycero-phosphocholine: dipalmitoyl-DL-alpha-phosphatidyl-L-serine:cholesterol (7:4:7 molar ratio). This phospholipid mixture was also assayed for brain conjugated diene levels in rats, since this parameter is an index of lipid peroxidation in rat cerebral cortex during post-ischaemic reperfusion. A citicoline-loaded phospholipid mixture has produced an increase in rat survival rate of about 24% and a reduction in diene levels of 60%, compared to the free drug.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Blood-Brain Barrier; Brain Ischemia; Cerebral Cortex; Cholesterol; Chromatography, High Pressure Liquid; Cytidine Diphosphate Choline; Disease Models, Animal; Drug Carriers; Drug Compounding; Drug Delivery Systems; Drug Evaluation; Lactates; Lactic Acid; Lipid Peroxidation; Liposomes; Male; Phosphatidylserines; Rats; Rats, Wistar; Reperfusion Injury; Survival Rate