Modulation of amphotericin B activity by association with mannose ester.
The biological and molecular properties of a new formulation of Amphotericin B complexed with the surfactant palmitoyl mannose were studied in in vitro as well as in in vivo situations. The properties analyzed include toxicity towards two types of mammalian cells and four fungi strains, effect on macrophage activity, inflammatory properties, acute toxicity in mice and spectral behavior in presence of foetal calf serum or 6% propanol. The results demonstrate that, in presence of palmitoyl mannose, the cytotoxicity of AmB is decreased towards both, fungal and mammalian cells while its fungistatic potential is increased, its inflammatory properties are conserved and its acute toxicity is significantly diminished. These effects can be potentially explained by the formation of a complex between AmB and the sugar ester that impedes the interaction of the drug with either serum components or cell membrane constituents. The overall properties of AmB in the complex would be expected to favor an increase in the immunoadjuvant properties of the drug, a more localized inflammation during fungal infection and consequently a better therapeutic efficiency.
Rocheleau
H
H
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Canada.
Saint-Germain
G
G
Barwicz
J
J
Gruda
I
I
Thérien
H M
HM
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008358:Mannose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013053:Spectrophotometry
D003902:Detergents; C091177:palmitoyl mannose; D000666:Amphotericin B; D006861:Hydrogen Peroxide; D008358:Mannose