THERMOSENSITIVE STERICALLY STABILIZED LIPOSOMES - FORMULATION AND IN-VITRO STUDIES ON MECHANISM OF DOXORUBICIN RELEASE BY BOVINE SERUM AND HUMAN PLASMA

Purpose. To formulate thermosensitive sterically stabilized liposomes and to study the effects of plasma and serum components in vitro. Meth ods. The rate of release of encapsulated doxorubicin (Dox) from liposo mes of various compositions was followed by fluorometric assay at 37 d egrees, 42 degrees and 45 degrees C, in buffer and also in both calf s erum and human plasma up to 50% by volume. Results. The optimal compos ition for the maximal differential release of doxorubicin between 37 d egrees C and 42 degrees C in human plasma was a mixture of dipalmitoyl phosphatidylcholine/hydrogenated say phosphatidylcholine/cholesterol a nd distearoylphosphatidylethanolamine derivatized with polyethylene gl ycol at a molar ratio of 100:50:30:6. In experiments designed to study the mechanism causing increased permeability of liposomes in bovine s erum, we found two different distinct release patterns: a slow linear rise of rate of Dox release far fluid liposomes and fast exponential r ise reaching plateau within 5 minutes for solid phase (rigid) liposome s. This release of Dox from rigid but not fluid liposomes was inhibite d by pre-heating serum at 55 degrees C for 30 minutes or by addition o f EDTA (but not EGTA) or antiserum to the C3 component of complement. Conclusions. A formulation of sterically stabilized liposomes with the proper thermal sensitivity in human plasma has been obtained. In addi tion, the results suggest that complement may play an important role i n the interaction of rigid but not fluid liposomes with bovine serum. Human plasma did not show this effect.