EFFECT OF HYPEROSMOLAR MANNITOL ON THE DELIVERY OF HIGH-MOLECULAR-WEIGHT SUBSTANCES ENTRAPPED IN LIPOSOMES TO THE BRAIN AND CULTURED C6 GLIOMA-CELLS

The effect of intravenous hyperosmolar mannitol on delivery of liposom es to the brain was investigated. Pure cAMP phosphodiesterase was iodi nated and entrapped in either dehydration-rehydration vesicles or smal l unilamellar vesicles composed of egg phosphatidylcholine, cholestero l, and sulfatides. A time-course study of liposomal delivery to the br ain after hyperosmolar mannitol administration showed increased delive ry to the brain of dehydration-rehydration vesicles and of small unila mellar 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 mo rphine-BSA entrapped in small unilamellar vesicles further confirmed t he delivery of liposomal contents to the brain, liver, and cultured gl ioma cells under hyperosmolar conditions. These data show that 2 M man nitol is able to reversibly disrupt the blood-brain barrier and thereb y increase the delivery of both free and liposomally-entrapped substan ces to the brain.