Polyene antibiotic amphotericin B in monomolecular layers: spectrophotometric and scanning force microscopic analysis

Abstract

Monolayers of amphotericin B (AmB) and monolayers composed of AmB and dipalmitoylphosphatidylcholine (DPPC) were formed at the argon^water interface and deposited on a solid support by means of the Langmuir^Blodgett technique. The hypsochromic shift observed in the absorption spectra of monolayers is indicative of aggregated structures of AmB. The exciton splitting theory allowed us to calculate the distance between neighboring molecules in the aggregates as 7.8 A î . Scanning force microscopy of the AmB monolayers revealed the formation of a homogeneous monolayer composed of molecules separated by a distance of 6^8 A î . Microscopy also reveals the formation of cylindrical structures of AmB with a diameter close to 17 A î (internal diameter close to 6 A î ) in the monolayers containing additionally 10 mol% DPPC. ß

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

“…It appeared that a laterally-oriented pool was particularly large in the membranes containing ergosterol and that such orientation of the drug had strongest effect on the membrane organization [13]. According to our earlier studies, AmB is able to form hydrophilic pores which can disturb transmembrane ion transport [16], indeed, but the results of the most recent studies, outlined above, seem to suggest that molecular mode of action of AmB with respect to biomembranes is primarily based on interference with the structural and dynamic properties of the lipid bilayers. This hypothesis requires further verification.…”

Organization of polyene antibiotic amphotericin B at the argon–water interface

“…Co. AmB was dissolved in 40% 2-propanol and then centrifuged for 15 min at 15 000 x g in order to remove micro crystals of the drug still remaining in the sample. presented by us previously [10,12,37]. Light absorption measurements and linear dichroism measurements were carried out with a Diode array UV-Vis spectrophotometer HP 8453.…”

“…7B, inset a). The formation of such structures in the monomolecular layers has been observed in the monomolecular layers, by means of scanning force microscopic analysis [10].…”

“…The ability of AmB molecules to form cylindrical structures that can play possibly the role of membrane pores, gained support from the theoretical studies carried out with application of the electrostatic interaction analysis [5], molecular dynamics approach [6][7][8] and from the experimental studies on ion permeability [9]. The ability of AmB to form ring-shaped molecular aggregates has been demonstrated by the scanning force microscopic analysis of monomolecular layers of the drug [10]. On the other hand, the results of recent experiments carried out with application of the 1 H-NMR [11] and FTIR [12] techniques demonstrated that the principal site of localization of AmB with respect to the lipid membrane is the polar headgroup region.…”

Anomalously high aggregation level of the polyene antibiotic amphotericin B in acidic medium: Implications for the biological action

“…Owing to the amphiphilic molecular structure AmB is able to self-organize into molecular aggregates both in water phase and in the hydrophobic core of the lipid membranes [3][4][5][6][7]. In the latter case, AmB is postulated to self-aggregate into the hydrophilic pores that may severely affect transmembrane ion transport [8][9][10]. On the other hand, the results of the recent structural studies show that the pharmacological effect of AmB towards the membranes may be associated with modification of structural and dynamic properties of the lipid bilayer [11][12][13][14].…”