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Method for loading lipsomes with ionizable phosphorylated hydrophobic compounds, pharmaceutical preparations and a method for administering the preparations

Patent ·
OSTI ID:879398

A method of entrapping ionizable compounds, preferably phosphorylated hydrophobic compounds, into liposomes having transmembrane gradients is disclosed. The procedures involve forming liposomes in an acidic medium or a basic medium, adding to the acidic medium a cationic compound or to the basic medium an anionic compound and then adding a base to the cationic-containing medium or an acid to the anionic-containing medium, thereby inducing the ionizable compound into the liposomes' internal aqueous phase. The compound-entrapped liposomes prepared in accordance with the disclosed methods may be used as pharmaceutical preparations. Methods of administering such pharmaceutical preparations are also disclosed.

Research Organization:
Lawrence Berkeley National Laboratory
DOE Contract Number:
AC03-76SF00098
Assignee:
The Reagents of the University of California (Oakland, CA)
Patent Number(s):
US 5,827,532
Application Number:
08/791557
OSTI ID:
879398
Country of Publication:
United States
Language:
English

References (19)

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The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice journal February 1983
Nonmediated Flip-Flop of Anionic Phospholipids and Long-Chain Amphiphiles in the Erythrocyte Membrane Depends on Membrane Potential journal September 1997
Measurement of Transmembrane Potentials in Phospholipid Vesicles journal June 1972
Determination of the electric potential at the external and internal bilayer-aqueous interfaces of the human erythrocyte membrane using spin probes journal August 1983
Techniques for encapsulating bioactive agents into liposomes journal June 1986
Pyranine as a sensitive pH probe for liposome interiors and surfaces. pH gradients across phospholipid vesicles journal May 1978
Membrane Transport of Sugars and Amino Acids journal June 1984
Uptake of safranine and other lipophilic cations into model membrane systems in response to a membrane potential journal January 1985
Light-induced proton gradients and internal volumes in chromatophores of Rhodopseudomonas sphaeroides journal November 1984
Preparation and characteristics of lipid vesicles journal December 1971
[43] Light-induced pH gradients measured with spin-labeled amine and carboxylic acid probes: Application to Halobacterium halobium cell envelope vesicles book January 1982
Bioenergetic Studies of Cells with spin Probes journal December 1983
Catecholamine uptake and concentration by liposomes maintaining pH gradients journal November 1976
Active proton uptake by chromaffin granules: observation by amine distribution and phosphorus-31 nuclear magnetic resonance techniques journal March 1977
Transbilayer transport of phosphatidic acid in response to transmembrane pH gradients journal February 1991
Taxoids: New Weapons against Cancer journal June 1996
NMR studies of pH-induced transport of carboxylic acids across phospholipid vesicle membranes journal March 1977

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