Serial MRI study of the enhanced therapeutic effects of liposome-encapsulated citicoline in cerebral ischemia

• Published in: International journal of pharmaceutics 2011-02, Vol.405 (1), p.228-233
• Main Authors: Ramos-Cabrer, Pedro, Agulla, Jesús, Argibay, Bárbara, Pérez-Mato, María, Castillo, José
• Format: Article
• Language: English
• Subjects: animal models; Animals; bioavailability; Biological and medical sciences; brain; Brain - drug effects; Brain - pathology; Brain - physiopathology; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Brain Ischemia - physiopathology; CDP-choline; Cerebral Infarction - drug therapy; Cerebral Infarction - pathology; Cerebral Infarction - physiopathology; Citicoline; Cytidine Diphosphate Choline - administration & dosage; Cytidine Diphosphate Choline - therapeutic use; Disease Models, Animal; Dose-Response Relationship, Drug; edema; encapsulation; General pharmacology; infarction; Infarction, Middle Cerebral Artery - veterinary; Injections, Intraperitoneal; Injections, Intravenous; intravenous injection; ischemia; Liposomes; Magnetic Resonance Imaging; Male; Medical sciences; MRI; Nootropic Agents - administration & dosage; Nootropic Agents - therapeutic use; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Stroke; Stroke - drug therapy; Stroke - pathology; Stroke - physiopathology; surgery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.12.014

Liposome encapsulation of active principles enhances their bioavailability to the brain. We investigated whether encapsulation of citicoline in liposomes increases its therapeutic effects in ischemia, performing a longitudinal MRI study of lesion volumes and edema in an animal model of stroke. Nineteen rats were submitted to permanent occlusion of the middle cerebral artery and treated with: (1) saline, (2) intraperitoneal citicoline (500 mg/kg), (3) intravenous citicoline (48 mg/kg), and (4) intravenous liposome-encapsulated citicoline (48 mg/kg). Lesion volumes were measured by MRI at days 0, 1, 3 and 7 following surgery. Encapsulation in liposomes increased the therapeutic effects of citicoline, as reflected by a 32% reduction of the infarct sizes at day 7, in contrast with controls where infarct sizes at day 7 increased by 39%, respect to values at day 0. Intravenously injected citicoline reduced infarct sizes by 9% while intraperitoneal citicoline resulted in an increase of infarct sizes by 10%. A slight (not significant) reduction of edema formation was observed for animals treated with citicoline, in all of its delivery forms. Liposome-encapsulated citicoline causes a noticeable reduction in lesion volumes as compared to free citicoline (either i.p. or i.v.) at days 1, 3 and 7 following permanent stroke.