Effects of the aggregation state of amphotericin B on its toxicity to mice

Barwicz, Joanna; Christian, Sylvie; Gruda, Ilona

doi:10.1128/aac.36.10.2310

Cited by 159 publications

(140 citation statements)

References 17 publications

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“…The use of AmB is limited by several side effects, including nephrotoxicity and hemolytic activity; therefore much effort has been made to develop formulations able to reduce its toxicity and increase its therapeutic effect (Brajtburg and Bolard 1996;Torrado et al 2008). Both the therapeutic and toxic effects of AmB seem to be related to its state of aggregation, and the monomeric state of AmB is usually ascribed as the less toxic state (LamyFreund et al 1989;Bolard et al 1991;Barwicz and Tancrede 1997;Barwicz et al 1992;Legrand et al 1992). In this context, sonicated DODAB bicelles have been found to be able to solubilize mainly monomeric AmB molecules (Vieira and Carmona-Ribeiro 2001) and display low nephrotoxicity (Lincopan et al 2005).…”

Section: Detecting Dodab Bicelles By Esrmentioning

confidence: 99%

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

et al. 2017

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Cationic bilayers have been used as models to study membrane fusion, templates for polymerization and deposition of materials, carriers of nucleic acids and hydrophobic drugs, microbicidal agents and vaccine adjuvants. The versatility of these membranes depends on their structure. Electron spin resonance (ESR) spectroscopy is a powerful technique that employs hydrophobic spin labels to probe membrane structure and packing. The focus of this review is the extensive structural characterization of cationic membranes prepared with dioctadecyldimethylammonium bromide or diC14-amidine to illustrate how ESR spectroscopy can provide important structural information on bilayer thermotropic behavior, gel and fluid phases, phase coexistence, presence of bilayer interdigitation, membrane fusion and interactions with other biologically relevant molecules.

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Section: Detecting Dodab Bicelles By Esrmentioning

confidence: 99%

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

et al. 2017

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“…Such structures of AmB, formed in the environment of biomembranes are able to disturb severely physiological ion transport and are believed to be responsible for pharmaceutical activity of the drug. The analysis of the spectral shifts have been very frequently applied to study molecular organization of AmB [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. The approach applied in the present work enables to link the spectral changes in the electronic absorption spectra with defined molecular organization patterns.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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

Gagoś¹,

Gruszecki²

2008

Biophysical Chemistry

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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.

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“…The importance of the aggregation state and particle size of amphotericin B under physiologic conditions and the effects on activity and toxicity have been established, [25][26][27][28] as well as the interaction between amphotericin B and the biological milieu. 29 By altering the formulation of amphotericin B, it is possible to manipulate these properties to reduce toxicity and improve uptake and efficacy.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

Yardley¹,

Croft²

1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The activities of four amphotericin B formulations, Fungizone , AmBisome , Amphocil , and Abelcet , were compared in vitro and in vivo against Trypanosoma cruzi infections. In vitro, Fungizone and Amphocil were highly active against T. cruzi Y strain amastigotes in macrophages with 50% effective dose (ED 50 ) values of 0.027-0.028 g/ml, which were 7-fold and 42-fold more active than AmBisome and Abelcet, respectively. In vitro activities of all formulations against T. cruzi amastigotes in Vero cells were similar, with ED 50 values in the range of 2.0-4.2 g/ml. Acute infections of the T. cruzi Y strain in BALB/c mice were suppressed in all animals by a single 25 mg/kg dose of the liposomal formulation AmBisome. At the same dose, the two other lipid formulations, Amphocil and Abelcet, increased the survival rate but did not suppress infection in all animals.

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Effects of the aggregation state of amphotericin B on its toxicity to mice

Cited by 159 publications

References 17 publications

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

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

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

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