Enhanced therapeutic effect of cytidine-5'-diphosphate choline when associated with GM1 containing small liposomes as demonstrated in a rat ischemia model.

PURPOSE: Cytidine-5'-diphosphate choline (CDPc) was encapsulated in long-circulating unilamellar vesicles (SUVs) to improve the drug's biological effectiveness.
METHODS: SUVs made up of diaplmitoylphosphatidylcholine/diaplmitoylphosphatidylserine /cholesterol (7:4:7 molar ratio) and 8 mol % of ganglioside GM1 were prepared by extrusion through polycarbonate filters (mean diameter 50 nm). The formulation effectiveness was evaluated by an in vivo model of cerebral ischemia on Wistar rats.
RESULTS: The enhanced delivery of CDPc into the brain improved the therapeutic effectiveness of the drug. CDPc-loaded SUVs improved the survival rate of ischemized and reperfused Wistar rats (320-350 g) by approximately 66% compared with the free drug. Liposome formulation was also able to effectively protect the brain against peroxidative damage caused by post-ischemic reperfusion. SUVs lowered the conjugated diene levels of the cerebral cortex. The liposomal delivery system did not alter the distribution patterns in the various cerebral lipid fractions of the drug, radiolabeled with 14C-CDPc.
CONCLUSIONS: CDPc-loaded SUVs were able to protect the brain against damage induced by ischemia. A possible clinical application is envisaged.