Suppression of experimental allergic encephalomyelitis (EAE) with liposome-encapsulated protease inhibitor: therapy through the blood-brain barrier.

Experimental allergic encephalomyelitis (EAE) is an experimentally induced autoallergic demyelinating disease which is caused by immunization with a particular neuroantigen, such as myelin basic protein (MBP). Results have suggested that protease inhibitors might be useful therapeutically. Leupeptin (acetyl-L-leucyl-L-leucyl-argininal), a protease inhibitor of tripeptide nature, was effective in suppressing EAE in guinea pigs, when administered in a form of liposomes consisting of egg lecithin, cholesterol and sulfatide. The drug seemed to be transported into the central nervous system (CNS) tissues across the blood-brain barrier with the aid of a particular type of liposomes as vehicle. Some outbred Hartley guinea pigs completely recovered from distinct symptoms of EAE, such as loss of weight, paralysis, incontinence and/or diarrhea, when treated i.p. every day with lecithin-cholesterol-sulfatide (molar ratio, 4:5:1) reverse-phase evaporation vesicles-encapsulated leupeptin (REV-Leu) from day 6 after sesitization with 30 micrograms of bovine MBP. Scarcely any typical histopathological changes of EAE were found in the CNS of most survivors treated with REV-Leu.