ABSTRACT
A clue as to the direction to take came from a review of the red blood cell literature, which revealed that one of the factors associated with the long circulation half-lives of erythrocytes was the presence of sialic acid on the erythrocyte surface. Desialation of erythrocytes led to their rapid removal from circulation into the MPS. After a futile attempt to make long circulating liposomes from totallipids extracted from red blood cells, we turned our attention to the family of sialated glycolipids (gangliosides) present on the surface of red blood cells. It soon became apparent that incorporation of 7 to 10 mol% monosialoganglioside GMl into egg phosphatidylcholine:cholesterol (PC:CH, 2: 1) liposomes increased their circulation half-
lives, although only modestly. The first public presentation of this work was at the NATO Advanced Study Institute on "Targeting of Drugs with Synthetic Systems" in 1985. We subsequently observed that inclusion of solid-phase phospholipids in the liposomes further increased their circulation half-lives and the first paper on GM1-containing long circulating liposomes was published in 1987.2 This was followed closely by an independent publication by Gabizon and Papahadjopoulos showing that not only did GMI-containing liposomes have increased circulation half-lives, but they also resulted in increased uptake into solid tumors.3 The stage was now set to look at therapeutic applications of these new formulations of long circulating liposomes, which were termed Stealth® liposomes (S-liposomes).4 The term "Stealth liposomes", implying the ability of the new liposomes to avoid detection by the cells of the MPS, was coined by Dr. Frank Martin of Liposome Technology, Inc., and has an analogy in the military term "stealth bomber" referring to an aircraft which avoids detection by enemy radar.
