Abstract
The human toxicity of amphotericin B can be considerably reduced by associating the drug with liposomes of varying lipid compositions. Some lipid compositions are much more effective than others. We show that a simple kinetic fluorescence assay using pyranine as an indirect probe of amphotericin-induced K + currents may be used to study different liposomal drug delivery systems in vitro. We find that lipid mixtures composed of DMPC/DMPG/amphotericin at a 7:3:1 mole ratio show very slo functional delivery with a preference for ergosterol over cholesterol-containing membrane vesicles. On the other hand, amphotericin delivered from egg phosphatidylcholine liposomes lead to 100-fold increases in K + leakage at one-fifth the amphotericin concentration of the 7:3:1 system. The egg phosphatidylcholine system as well as micellar amphotericin also show a slight selectivity towards cholesterol-containing vesicles over ergosterol. These results are consistent with previous clinical and in vitro cellular studies and this technique may prove valuable in screening of other delivery systems.
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