PLASMA DEPENDENT PH SENSITIVITY OF LIPOSOMES CONTAINING SULFATIDE

In this study we investigated the possibility to define relatively pla sma-stable liposomal preparations in which the sensitivity to moderate drops of pH (i.e., from 7.4 to 6.8) would be induced by the presence of plasma itself. The liposome stability was monitored by determining the release of entrapped 5,6-carboxyfluorescein (CF). Using small unil amellar vesicles composed of egg phosphatidylcholine (EPC) and bovine brain sulfatide (CS) (4 : 1, molar ratio), the amount of CF released a t pH 6.8 in the presence of 50% plasma was 3-fold that at pH 7.4, wher eas no significant differences in the amount of CF released were obser ved when the same liposomes were incubated in buffer at pH 7.4 and 6.8 , respectively. The increase in plasma induced leakage as a consequenc e of a drop in the pH medium, seems to specifically depend on the pres ence of sulfatide molecule in the bilayer since neither the acidic cho lesterol 3-sulfate nor galactocerebroside, are able to induce pH sensi tivity in EPC liposomes. Of all the plasma components considered (VLDL , LDL, HDL, protein fraction), VLDL seemed preferentially involved in the pH sensitivity induced by CS since they promoted an almost complet e release of CF from EPC/CS small unilamellar vesicles. Thus, these li posomes are potentially a useful tool for a specific drug delivery to those pathological tissues such as tumors, inflammation sites and isch emic areas in which it is known that a lowering of the pH can occur.