Title:Super aggregated form of Amphotericin B: a novel way to increase its therapeutic index
Volume: 22
Issue: 7
Author(s): Qamar Zia, Asim Azhar, Mohammad Amjad Kamal, Gjumrakch Aliev, Mohammad Owais and Ghulam Md Ashraf
Affiliation:
Keywords:
Amphotericin B, bio-distribution, spectroscopy, super-aggregate, toxicity.
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 selfassociated
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.
