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

Abstract

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.