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

Abstract

Amphotericin B (AmB) is a life-saving antibiotic, used to treat deep-seated mycotic infections. Both the therapeutic and toxic side effects of AmB are directly dependent on its molecular organization. Organization of AmB was studied in monocomponent monomolecular layers formed at the argon-water interface, by means of polarized and nonpolarized electronic absorption spectroscopy and analyzed in terms of the exciton splitting theory. The results provide direct indication that AmB forms spontaneously dimers that can be assembled into molecular structures characterized by homogeneous orientational distribution in the monolayer, interpreted as cylindrical pores. The structures are not stable at surface pressures higher than 20 mN/m and therefore dimers are concluded as abundant molecular organization forms of AmB in biomembranes. Possibility of stabilization of the cylindrical structures, at higher surface pressures, by other molecules, eg. sterols, is also discussed.

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

“…AmB monomers and dimers are believed to bear most powerful potential in severely disturbing physiological biomembranes activity: monomers, owing to the amphiphilic character of the molecule (see Fig. 1) that can not fit into the lipid membrane without disturbing its organization and dimers owing to the potential of formation of hydrophilic membrane channels [20]. In our opinion, such a finding sheds light on the molecular mechanisms of selectivity of AmB towards the biomembranes of fungi and opens new perspectives in preparation of formulations with enhanced therapeutic effect.…”

“…film [20]. Interestingly, very recent reports show that, most probably, more complex molecular structures of the drug are formed out of dimers [21].…”

“…A C C E P T E D M A N U S C R I P T slightly allowed [20,21]. This provides possibility to excite all the molecular organization forms of AmB at wavelengths longer than 390 nm.…”

Interactions of bioactive molecules & nanomaterials with Langmuir monolayers as cell membrane models

“…To address this issue, Langmuir monolayers have been used involving AmB alone as well as mixed with membrane sterols. The pressure-area isotherm of AmB revealed its conformational changes from a horizontal to a vertical position upon compression [123,124], later confirmed with BAM [125] and ATR-FTIR spectroscopy [130,131] for Langmuir films.…”

“…In situ light absorption measurements of AmB in monolayers revealed spontaneous formation of aggregates (dimers) upon compression. An analysis in terms of exciton splitting indicated formation of cylindrically aggregated AmB molecules, creating a pore-like structure [130].…”