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

• Main Authors: Clement John G, Zhao Jinying, Wasan Ellen K, Gershkovich Pavel, Bartlett Karen, Lee Jinkyung, Leon Carlos G, Wasan Kishor M
• Format: Article
• Language: English
• Published: BMC 2011-08-01
• Series: Lipids in Health and Disease
• Subjects: Amphotericin B; Candida; cytotoxicity; monocytes.
• Online Access: http://www.lipidworld.com/content/10/1/144

<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>show less nephrotoxicity and enhanced solubility compared to Fungizone™ a commercial AmpB formulation.</p> <p>The purpose of this study was to determine the cytotoxicity of Fungizone™, Ambisome™ and two novel AmpB formulations (iCo-009 and iCo-010) against <it>Candida albicans</it>, human kidney (293T) cells and monocytic (THP1) cells.</p> <p>Methods</p> <p>Cell cytotoxicity to the AmpB formulations was evaluated by MTS and LDH assays. <it>In vitro </it>anti-<it>Candida albicans </it>activity was assessed after a 48 h drug incubation.</p> <p>Results</p> <p>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).</p> <p>The calculated EC50 to <it>Candida albicans </it>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).</p> <p>Conclusions</p> <p>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 <it>Candida albicans </it>model.</p> <p>The absence of cytotoxicity as well as its higher efficacy for the <it>Candida </it>model compared to Fungizone™ and Ambisome™ suggest that iCo-010 has potential in treating candidiasis.</p>