A kinetic method for measuring functional delivery of amphotericin B by drug delivery systems.
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.
Peterson
R P
RP
Department of Chemistry, University of Wisconsin-Eau Claire 54702.
Benz
S K
SK
Whyte
B S
BS
Hartsel
S C
SC
D000666:Amphotericin B / Q000008:administration & dosage*; D001190:Arylsulfonates; D002784:Cholesterol; D004337:Drug Carriers; D004875:Ergosterol; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008081:Liposomes; D010713:Phosphatidylcholines / Q000302:isolation & purification
D001190:Arylsulfonates; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D000666:Amphotericin B; D002784:Cholesterol; C005047:pyranine; D004875:Ergosterol