A kinetic method for measuring functional delivery of amphotericin B by drug delivery systems

• Published in: Biochimica et biophysica acta Vol. 1064; no. 1; p. 165
• Main Authors: Peterson, R P, Benz, S K, Whyte, B S, Hartsel, S C
• Format: Journal Article
• Language: English
• Published: Netherlands 26.04.1991
• Subjects: Amphotericin B - administration & dosage; Arylsulfonates; Cholesterol; Drug Carriers; Ergosterol; Hydrogen-Ion Concentration; Kinetics; Liposomes; Phosphatidylcholines - isolation & purification
• ISSN: 0006-3002; 1878-2434
• DOI: 10.1016/0005-2736(91)90424-7

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 slow 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.