title: Super aggregated form of Amphotericin B: a novel way to increase its therapeutic index.
abstract: Amphotericin B (AmB)-deoxycholate micellar formulation, Fungizone®, is the drug of choice for the treatment of unidentified mycotic infections. However, it usage has been marred by long therapeutic regimes and severe side effects. The less toxic lipid associated AmB formulations have been limited by their high expense, with some loss in activity. The quest for decreasing AmB cytotoxicity as well as production cost has resulted in the development of AmB super-aggregate as an alternative to its existing lipid formulations. AmB super-aggregate is spectroscopically distinct from the aggregate present in Fungizone, displaying enhanced thermodynamic stability. The poly-aggregated form of AmB exhibits reduced toxicity in mammalian cells in vitro and to mice in vivo, while maintaining its 'gold standard' antifungal activity. Poly-aggregated AmB interacts predominantly with serum albumin and also attenuates its ability to induce potentially harmful cytokines. Bio-distribution studies have demonstrated that the self-associated AmB shows greater accumulation in reticulo-endothelial organs while sparing kidney, one of the principal organs where its toxic effects are seen. The super-aggregated AmB can thus be used to improve the therapeutic index of AmB against a plethora of fungal infections including candidiasis and cryptococcosis, thus providing a fitting solution to growing demand of an active, less toxic substitute of AmB.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Zia
authors.forename: Asim
authors.initials: A
authors.lastname: Azhar
authors.forename: Mohammad Amjad
authors.initials: MA
authors.lastname: Kamal
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
authors.forename: Mohammad
authors.initials: M
authors.lastname: Owais
authors.affiliation: Department of Biotechnology, Gagan College of Management and Technology, Aligarh, India Aligarh, India. gashraf@kau.edu.sa.
authors.forename: Ghulam Md
authors.initials: GM
authors.lastname: Ashraf
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D012709:Serum Albumin / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D004338:Drug Combinations; D012709:Serum Albumin; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination