TY - JOUR
T1 - Generation of pH-Sensitive Liposomes
T2 - Use of Large Unilamellar Vesicles Containing N-Succinyldioleoylphosphatidylethanolaminet
AU - Nayar, Rajiv
AU - Schroit, Alan J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1985/10/1
Y1 - 1985/10/1
N2 - By use of a carboxylated derivative of phosphatidylethanolamine, N-succinyldioleoyl-phosphatidylethanolamine (COPE), pH-sensitive liposomes have been designed that have a wide range of leakage properties. The leakage rate of the vesicle contents, as determined by the release kinetics of the water-soluble fluorophore 8-aminonaphthalene-l,3,6-trisulfonic acid complexed with the quencher p-xylenebis(pyridinium) dibromide [Ellens, H., Bentz, J., & Szoka, F. C. (1984) Biochemistry 23, 1532], was found to be dependent on the lipid composition and the pH of the incubation medium. Pure COPE vesicles released their encapsulated contents at pH 7.4 but not at pH 4.0. Leakage of these vesicles appears to be due to the electrostatic interactions between the COPE molecules. A dramatic reversal of the leakage properties was observed in mixed-lipid vesicles composed of COPE containing increasing amounts of dioleoylphosphatidylethanolamine (DOPE). Unlike pure COPE vesicles, COPE/DOPE (3:7) vesicles were more leaky under acidic conditions (pH 4.0) than they were at neutral pH. Studies employing a fluorescent COPE analogue, N-succinyl-1-acyl-2-[6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]caproyl]phosphatidylethanolamine, suggested that the mechanism of leakage might be a result of lipid-packing defects due to the nonbilayer properties of DOPE and protonation of the COPE molecules. Hence, the mechanism of release is different from that of other recently described pH-sensitive liposomes where either fusion or aggregation of the vesicles results in the release of vesicle contents.
AB - By use of a carboxylated derivative of phosphatidylethanolamine, N-succinyldioleoyl-phosphatidylethanolamine (COPE), pH-sensitive liposomes have been designed that have a wide range of leakage properties. The leakage rate of the vesicle contents, as determined by the release kinetics of the water-soluble fluorophore 8-aminonaphthalene-l,3,6-trisulfonic acid complexed with the quencher p-xylenebis(pyridinium) dibromide [Ellens, H., Bentz, J., & Szoka, F. C. (1984) Biochemistry 23, 1532], was found to be dependent on the lipid composition and the pH of the incubation medium. Pure COPE vesicles released their encapsulated contents at pH 7.4 but not at pH 4.0. Leakage of these vesicles appears to be due to the electrostatic interactions between the COPE molecules. A dramatic reversal of the leakage properties was observed in mixed-lipid vesicles composed of COPE containing increasing amounts of dioleoylphosphatidylethanolamine (DOPE). Unlike pure COPE vesicles, COPE/DOPE (3:7) vesicles were more leaky under acidic conditions (pH 4.0) than they were at neutral pH. Studies employing a fluorescent COPE analogue, N-succinyl-1-acyl-2-[6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]caproyl]phosphatidylethanolamine, suggested that the mechanism of leakage might be a result of lipid-packing defects due to the nonbilayer properties of DOPE and protonation of the COPE molecules. Hence, the mechanism of release is different from that of other recently described pH-sensitive liposomes where either fusion or aggregation of the vesicles results in the release of vesicle contents.
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U2 - 10.1021/bi00342a042
DO - 10.1021/bi00342a042
M3 - Article
C2 - 4084501
AN - SCOPUS:0022377524
SN - 0006-2960
VL - 24
SP - 5967
EP - 5971
JO - Biochemistry
JF - Biochemistry
IS - 21
ER -