CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke.
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.
Adibhatla
Rao Muralikrishna
RM
Department of Neurological Surgery, H4-330, Clinical Science Center, University of Wisconsin-Madison, Madison, WI 53792-3232, USA. adibhatl@neurosurg.wisc.edu
Hatcher
J F
JF
Tureyen
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000008:administration & dosage; D002794:Choline / Q000008:administration & dosage*; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D005677:G(M1) Ganglioside / Q000008:administration & dosage; D008081:Liposomes / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D010713:Phosphatidylcholines / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome
D004338:Drug Combinations; D008081:Liposomes; D010713:Phosphatidylcholines; D005677:G(M1) Ganglioside; D003566:Cytidine Diphosphate Choline; D002784:Cholesterol; D002794:Choline