Effect of phospholipid structure on stability and survival times of liposomes in circulation.

The phosphatidylcholine (PC) component of liposomes was structurally modified by replacing its C-1, or both C-1 and C-2, ester linkage(s) with an ether and/or carbamyl bond(s) or by changing its steric configuration. Small unilamellar liposomes were formed from PC, traces of the corresponding 14C-labeled PC and cholesterol in the presence of 6-carboxyfluorescein (02.M) by sonication, and purified by centrifugation. These liposomes were administered intravenously to rats, and their stability in blood as well as the rate of their clearance from the circulation were determined. Stability and survival times of liposomes were markedly increased by modifying both the C-1 and the C-2 ester linkages in PC. A similar but quantitatively smaller effect was observed when only the C-1 ester linkage was modified. However, the stability remained unaffected by changing the steric configuration of PC, but this modification influenced the clearance rate of liposomes from the circulation. These results demonstrate that both stability in blood and the clearance rate from circulation can be modulated by structurally modifying the ester linkages in the phospholipid component of liposomes.