Survival rate improvement in a rat ischemia model by long circulating liposomes containing cytidine-5'-diphosphate choline

Unilamellar liposomes made up of DPPC-DPPS-Chol (7:4:7 molar ratio) and ganglioside G(M1) 8% mol were used to deliver cytidine-5(I)-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.