Super aggregated form of Amphotericin B: a novel way to increase its therapeutic index

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.

Cite this article as:

Zia Qamar, Azhar Asim, Kamal Amjad Mohammad, Aliev Gjumrakch, Owais Mohammad and Ashraf Md Ghulam, Super aggregated form of Amphotericin B: a novel way to increase its therapeutic index, Current Pharmaceutical Design 2016; 22 (7) . https://dx.doi.org/10.2174/1381612822666151209151719