PMID: 8584472Oct 1, 1995Paper

Thermosensitive sterically stabilized liposomes: formulation and in vitro studies on mechanism of doxorubicin release by bovine serum and human plasma

Pharmaceutical Research
M H GaberD Papahadjopoulos

Abstract

To formulate thermosensitive sterically stabilized liposomes and to study the effects of plasma and serum components in vitro. The rate of release of encapsulated doxorubicin (Dox) from liposomes of various compositions was followed by fluorometric assay at 37 degrees, 42 degrees and 45 degrees C, in buffer and also in both calf serum and human plasma up to 50% by volume. The optimal composition for the maximal differential release of doxorubicin between 37 degrees C and 42 degrees C in human plasma was a mixture of dipalmitoylphosphatidylcholine/hydrogenated soy phosphatidylcholine/cholesterol and distearoylphosphatidylethanolamine derivatized with polyethylene glycol at a molar ratio of 100:50:30:6. In experiments designed to study the mechanism causing increased permeability of liposomes in bovine serum, we found two different distinct release patterns: a slow linear rise of rate of Dox release for fluid liposomes and fast exponential rise reaching plateau within 5 minutes for solid phase (rigid) liposomes. This release of Dox from rigid but not fluid liposomes was inhibited by pre-heating serum at 55 degrees C for 30 minutes or by addition of EDTA (but not EGTA) or antiserum to the C3 component of complement. A formulation ...Continue Reading

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