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Background  Invasive fungal infections such as candidiasis constitute an increasingly important medical problem. Drugs currently used for the treatment of candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B (AmpB) presents several limitations such as its nephrotoxicity and limited solubility. We have developed two novel lipid-based AmpB formulations which  in vivo  show less nephrotoxicity and enhanced solubility compared to Fungizone™ a commercial AmpB formulation.  The purpose of this study was to determine the cytotoxicity of Fungizone™, Ambisome™ and two novel AmpB formulations (iCo-009 and iCo-010) against  Candida albicans , human kidney (293T) cells and monocytic (THP1) cells.    Methods  Cell cytotoxicity to the AmpB formulations was evaluated by MTS and LDH assays.  In vitro  anti- Candida albicans  activity was assessed after a 48 h drug incubation.    Results  None of the AmpB formulations tested showed cytotoxicity against 293T cells. In the case of THP1 cells only Fungizone™ and Ambisome™ showed cytotoxicity at 500 μg/L (n = 4-10, p < 0.05).  The calculated EC50 to  Candida albicans  for the different formulations was as follows: 26.8 ± 2.9 for iCo-010, 74.6 ± 8.9 for iCo-009, 109 ± 31 for Ambisome™ and 87.1 ± 22 for Fungizone™ (μg of AmpB/L, n = 6-12, p < 0.05).    Conclusions  The AmpB formulations analyzed were not cytotoxic to 293T cells. Cytotoxicity in THP1 cells was observed for Fungizone™ and Ambisome™, but not with the novel AmpB formulations. iCo-010 had higher efficacy compared to other three AmpB formulations in the  Candida albicans  model.  The absence of cytotoxicity as well as its higher efficacy for the  Candida  model compared to Fungizone™ and Ambisome™ suggest that iCo-010 has potential in treating candidiasis.

lipids in health and disease

In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009 and iCo-010) against Candida albicans, human monocytic and kidney cell lines