Amphotericin B interactions with a DOPC monolayer. Electrochemical investigations.
A model lipid membrane consisting of a monolayer of dioleoyl phosphatidylcholine (DOPC) adsorbed onto a Hg electrode has been used to study the interaction between the lipid and different formulations of Amphotericin B (AmB) [Fungizone (FZ), Heated Fungizone (HFZ), and Abelcet]. The lipid organizational order was measured by electrochemical methods [capacitance and metal ion (Tl(+)) reduction], characterizing the change in lipid order due to interaction with the drug. The mean size and number density of pores formed in the monolayer were estimated by fitting the reduction current transients to a random array of microelectrode model. This method was shown sensitive for investigation of the interaction of drugs with the DOPC monolayer. Abelcet was found to have a smaller disruptive effect on lipid order than FZ and HFZ. The formulations used to solubilize the AmB were also studied. Sodium deoxycholate used as a solubilizer in FZ displayed significant influence on lipid order similar to that observed for Abelcet. The lipid complex, used in Abelcet, did not significantly perturb the DOPC monolayer order. The lipid complex used in Abelcet may have an annealing or healing effect that buffers the disruption possible due to AmB.
Stoodley
R
R
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
Shepherd
J
J
Wasan
K M
KM
Bizzotto
D
D
D000666:Amphotericin B / Q000737:chemistry* / Q000633:toxicity*; D000935:Antifungal Agents / Q000737:chemistry* / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D004563:Electrochemistry; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000633:toxicity*; D010715:Phosphatidylglycerols / Q000737:chemistry* / Q000633:toxicity*
D000935:Antifungal Agents; D004338:Drug Combinations; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B; C017251:1,2-oleoylphosphatidylcholine