Effect of Hyperosmolar Mannitol on the Delivery of High Molecular Weight Substances Entrapped in Liposomes to the Brain and Cultured C6 Glioma Cells

Abstract

The effect of intravenous hyperosmolar mannitol on delivery of liposomes to the brain was investigated. Pure CAMP phosphodiesterase was iodinated and entrapped in either dehydration-rehydration vesicles or small unilamellar vesicles composed of egg phosphatidyl-choline, cholesterol, and sulfatides. A time-course study of liposomal delivery to the brain after hyperosmolar mannitol administration showed increased delivery to the brain of dehydration-rehydration vesicles and of small unilamellar vesicles compared with their respective normal saline controls. Clearance of both free or liposomally-entrapped enzyme from the brain was slower under hyperosmolar conditions. Studies with FITC-BSA or morphine-BSA entrapped in small unilamellar vesicles further confirmed the delivery of liposomal contents to the brain, liver, and cultured glioma cells under hyperosmolar conditions. These data show that 2M mannitol is able to reversibly disrupt the blood-brain barrier and thereby increase the delivery of both free and liposomally-entrapped substances to the brain.