LIPOSOME SIALIDATION

THIS PROPOSAL IS TO DEMONSTRATE FEASIBILITY OF INSERTION OF SIALIC ACID MOLECULES INTO MEMBRANES OF LIPOSOMES CARRYING HEMOGLOBIN. THE LIPOSOMES MAY BE PROVIDED BY NAVY CONTRACTORS OR PREPARED BY OFFEROR ACCORDING TO CONTRACTORS' SPECIFICATIONS FOR FOMULATION. THE ADDED SIALIC ACID WILL PROTECT THE LIPOSOMES FROM CLEARANCE BY THE RETICULOENDOTHELIAL SYSTEM AND THEREBY INCREASE THE RESIDENCY TIME OF THE LIPOSOMES IN THE CIRCULATION. NATURALLY-OCCURRING MOLECULES CONTAINING SIALIC ACID, CHIEFLY GANGLIOSIDES, WILL BE UTILIZED INITIALLY FOR THIS PURPOSE. THESE MOLECULES ARE OF LOW INTRINSIC ANTIGENICITY AND INTERCALATED SPONTANEOUSLY INTO LIPOSOMES WITH THE FORMATION OF STABLE ASSOCIATIONS. THE SIALIC ACID-RICH CARBOHYDRATE PORTIONS ARE DIRECTED TO THE EXTERNAL, AQUEOUS ENVIRONMENT. MODEL COMPOUNDS SUCH AS GANGLIOSIDE MINICS THAT CONTAIN SIALIC ACID OR OTHER CHARGED GROUPS WILL THEN BE DEVELOPED FOR ECONOMICAL LARGE-SCALE PRODUCTION OF NONPYROGENIC, CLEARANCE-RESISTANT LIPOSOMES CONTAINING HEMOGLOBIN THAT ARE BOTH INVISIBLE TO IMMUNE SURVEILLANCE AND THAT RETAIN FULL OXYGEN-CARRYING CAPACITY.