"STEALTH" LIPOSOME ENCAPSULATED HEMOGLOBIN--LOW TOXICITY BLOOD SUBSTITUTE

THE OVERALL GOAL IS TO DEVELOP AN OXYGEN-CARRYING RED BLOOD CELL SUBSTITUTE TO REPLACE WHOLE BLOOD TRANSFUSIONS AND/OR AN OXYGEN-CARRYING PLASMA EXPANDER TO REPLACE PLASMA AND INTRAVENOUS FLUIDS USED TO TREAT TRAUMA VICTIMS. BY ENTRAPPING HEMOGLOBIN IN LONG-CIRCULATING "STEALTH " LIPOSOMES WHICH ARE DESIGNED TO BE LESS SUSCEPTIBLE TO PHAGOCYTOSIS BY THE RETICULOENDOTHELIAL SYSTEM (RES) THAN ORDINARY LIPOSOMES, WE HOPE TO DEVELOP AN OXYGEN-CARRYING SYSTEM THAT IS SUBSTANTIALLY LESS IMMUNOTOXIC THAN OTHER EXPERIMENTAL SYSTEMS UNDER DEVELOPMENT, SUCH AS ORDINARY LIPOSOMES. IN THE PRESENT PROGRAM, WE PLAN TO INVESTIGATE STEALTH LIPOSOME ENTRAPPED HEMOGLOBIN IN TERMS OF ITS PHARMACOKINETICS, SYSTEMIC TOXICITY, CYTOTOXIC EFFECTS AND IMPAIRMENT/BLOCKAGE OF THE RES. STEALTH LIPOSOMES CONTAIN POLYETHYLENE GLYCOL LLIPD DERIVATIVES WHICH SHIELD THESE LIPIS PARTICLES FROM RES RECOGNITION AND UPTAKE AND SIGNIFICANTLY INCREASE CIRCULATION TIME IN THE BLOODSTREAM. THE LONG-TERM OBJECT OF THIS PROGRAM IS THE DEVELOPMENT OF STEALTH LIPOSOME HEMOGLOBIN FORMULATIONS MEETING PHARMACEUTICAL STANDARDS WITH RESPECT TO SAFETY, EFFICAY, SHELF-LIFE AND MANUFACTURABILITY.