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.