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.
ACKNOWLEDGEMENT OF GOVERNMENT SUPPORT
This invention was made with Government support under Grant No. DE-AC03-76SF00098, awarded by the Department of Energy. The Government has certain rights in this invention