title: A photophysical study on the role of bile salt hydrophobicity in solubilizing amphotericin B aggregates.
abstract: Amphotericin B (AmB) is a highly effective antifungal agent and finds utility against a broad spectrum of fungal species. Bile salts are biocompatible biosurfactants, widely used as drug delivery media for many hydrophobic drugs. AmB in the colloidal suspension of sodium deoxycholate (NaDC) is a well-known commercial formulation of AmB. In the present work, the association of AmB with three bile salts, namely sodium cholate, sodium taurodeoxycholate and sodium taurocholate is studied using the photophysical properties of AmB. Selective excitation of monomeric AmB (lambda(ex) 414 nm, lambda(em) 560 nm) and dimeric AmB (lambda(ex) 335 nm, lambda(em) 472 nm) reveal that with increasing concentration of bile salts, the higher aggregates in water disaggregate to form both monomeric and dimeric forms of AmB. This is seen to be a general trend in all the bile salts studied. Results of steady state fluorescence anisotropy and fluorescence lifetimes studies suggest that the interaction between AmB (hydrophobic heptaene face) and bile salts (hydrophobic steroidal face) is essentially hydrophobic.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Madras, Chennai - 600 036, Tamilnadu, India.
authors.forename: Susithra
authors.initials: S
authors.lastname: Selvam
authors.forename: Maneesha Esther
authors.initials: ME
authors.lastname: Andrews
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000666:Amphotericin B / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D005454:Fluorescence Polarization; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008958:Models, Molecular; D015394:Molecular Structure; D009994:Osmolar Concentration; D055668:Photochemical Processes; D020358:Sodium Cholate / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism*; D013656:Taurocholic Acid / Q000737:chemistry / Q000378:metabolism; D013657:Taurodeoxycholic Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001647:Bile Acids and Salts; D008823:Micelles; D013501:Surface-Active Agents; D013657:Taurodeoxycholic Acid; D013656:Taurocholic Acid; D000666:Amphotericin B; D020358:Sodium Cholate