Membrane permeabilizing activity of amphotericin B is affected by chain length of phosphatidylcholine added as minor constituent

AbstractThe effect of acyl-chain length of phospholipid on the membrane permeabilizing activity of amphotericin B (AmB) was examined using egg phosphatidylcholine (eggPC) liposomes containing 5% or 20% phosphatidylcholine with various lengths of fatty acyl chains from C10 to C18; 1,2-dicapryloyl-sn-glycero-3-phosphocholine (DCPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The membrane activity of AmB was evaluated by two methods; the drug was added to a liposome suspension (added-via-aqua), or mixed with lipids prior to liposome preparation (mixed-with-lipid). In both cases, K+ influx by AmB was measured as pH change inside liposomes by 31P-NMR. The C10 and C12 acyl phospholipids markedly enhanced the activity of AmB, the C14 and C16 lipids virtually showed no effect, and the C18 lipid was inhibitory to the AmB's action. Clear distinction between the C12 and C14 lipids, which differ only in acyl chains by two carbons, implies that molecular interaction between phospholipid and AmB is partly due to the matching of their hydrophobic length