pH-sensitive liposomes: characterization and application

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:6791764

Connor, J

It has been demonstrated that liposomes composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoylhomocysteine (PHC) have the ability to fuse with adjacent membranes upon exposure to mildly acid pH. The ability of liposomes to fuse is absolutely dependent on the presence of DOPE and a weakly acidic amphiphile. The acid induced fusion event is a leaky process, but the leakage can be reduced by 50%, with only a small loss of fusion ability, by the inclusion of 40 mole percent cholesterol. Using an established monoclonal antibody targeting system. pH-sensitive immunoliposomes were prepared which successfully delivered entrapped calcein to the cytoplasm of target cells. The addition of chloroquine, which raises the internal pH of cellular vacuoles, blocks the cytoplasmic delivery of the pH-sensitive immunoliposomes. pH-insensitive immunoliposomes delivered calcein only to the endosome/lysosome system and not the cytoplasm. /sup 31/P-NMR and light scattering of DOPE:OA liposomes under acidic conditions demonstrate that the effect of the protons and the divalent cations is to force the DOPE to revert to the hexagonal II configuration. In vivo experiments with DOPE:OA immunoliposomes indicate that the liposomes rapidly aggregate and release their contents upon exposure to plasma. These results indicate that pH-sensitive immunoliposomes are an effective tool for in vitro cytoplasmic delivery but are ineffective for in vivo delivery at this point in development.

• Research Organization: Tennessee Univ., Knoxville (USA)
• OSTI ID: 6791764
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
LIPOSOMES
CYTOLOGY
NUCLEAR MAGNETIC RESONANCE
CALCIUM COMPOUNDS
CATIONS
CELL MEMBRANES
IN VITRO
MAGNESIUM COMPOUNDS
PH VALUE
PHOSPHOLIPIDS
PHOSPHORUS 31
ALKALINE EARTH METAL COMPOUNDS
BIOLOGY
CELL CONSTITUENTS
CHARGED PARTICLES
ESTERS
IONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
MAGNETIC RESONANCE
MEMBRANES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANOIDS
PHOSPHORUS ISOTOPES
RESONANCE
STABLE ISOTOPES
550301* - Cytology- Tracer Techniques