Amphotericin B Formulations and Drug Targeting

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

“…Its mechanism of action is supposed to be based on changes in membrane permeability (Bolard 1986;Fujii et al 1997;Cohen 2010), although a mechanism based on the production of free radicals has also been suggested (Lamy-Freund et al 1985;Sokol-Anderson et al 1988;Sangalli-Leite et al 2011). 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).…”

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

“…1) is a life saving polyene antibiotic used to treat deep-seated mycotic infections [1,2]. Despite very strong side effects and toxicity to patients AmB is constantly being applied owing to its pharmaceutical effectiveness [3].…”

“…Efforts of multiple research laboratories in the world are directed toward elaboration of a formulation of the drug characterized by minimized toxic side effects but still preserving the antibiotic activity toward fungi. In this respect, understanding of molecular mechanisms of biological action of AmB seems to be a primary target [1,2].…”

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

“…1 for a chemical structure) used to treat deep-seated mycotic infections [1,2]. 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].…”

“…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]. Despite the exact mode of action of AmB it is without doubt that both the pharmacological activity and the toxic side effects are strongly dependent on molecular organization of the drug in formulation [1,[15][16][17]. Several delivery systems and modifications of the antibiotic molecule have been elaborated to reduce the toxic side effects.…”