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Brain Res. 2005 Oct 5;1058(1-2):193-7.

CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke.

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1
Department of Neurological Surgery, H4-330, Clinical Science Center, University of Wisconsin-Madison, Madison, WI 53792-3232, USA. adibhatl@neurosurg.wisc.edu

Abstract

Cytidine-5'-diphosphocholine (CDP-choline, Citicoline, Somazina) is in clinical use (intravenous administration) for stroke treatment in Europe and Japan, while USA phase III stroke clinical trials (oral administration) were disappointing. Others showed that CDP-choline liposomes significantly increased brain uptake over the free drug in cerebral ischemia models. Liposomes were formulated as DPPC, DPPS, cholesterol, GM(1) ganglioside; 7/4/7/1.57 molar ratio or 35.8/20.4/35.8/8.0 mol%. GM(1) ganglioside confers long-circulating properties to the liposomes by suppressing phagocytosis. CDP-choline liposomes deliver the agent intact to the brain, circumventing the rate-limiting, cytidine triphosphate:phosphocholine cytidylyltransferase in phosphatidylcholine synthesis. Our data show that CDP-choline liposomes significantly ( P < 0.01) decreased cerebral infarction (by 62%) compared to the equivalent dose of free CDP-choline (by 26%) after 1 h focal cerebral ischemia and 24 h reperfusion in spontaneously hypertensive rats. Beneficial effects of CDP-choline liposomes in stroke may derive from a synergistic effect between the phospholipid components of the liposomes and the encapsulated CDP-choline.

PMID:
16153613
PMCID:
PMC1939829
DOI:
10.1016/j.brainres.2005.07.067
[Indexed for MEDLINE]
Free PMC Article
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