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
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
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DOI：
10.1186/1476-511x-10-144
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发表时间：
2011-08-20
影响因子：
4.5
通讯作者：
Wasan, Kishor M.
中科院分区：
文献类型：
--
作者：
Leon, Carlos G.;Lee, Jinkyung;Wasan, Kishor M.
背景：念珠菌病等侵袭性真菌感染构成了一个日益重要的医学问题。目前用于治疗念珠菌病的药物包括多烯类（如两性霉素B）和唑类。两性霉素 B (AmpB) 存在一些局限性，例如肾毒性和溶解度有限。我们开发了两种新型基于脂质的 AmpB 制剂，与商业 AmpB 制剂 Fungizone (TM) 相比，它们在体内表现出较低的肾毒性和增强的溶解度。本研究的目的是确定 Fungizone (TM)、Ambisome (TM) 和两种新型 AmpB 制剂（iCo-009 和 iCo-010）对白色念珠菌、人肾的细胞毒性 (293T) 细胞和单核细胞 (THP1) 细胞。方法：通过 MTS 和 LDH 测定评估细胞对 AmpB 制剂的细胞毒性。药物孵育 48 小时后评估体外抗白色念珠菌活性。结果：测试的 AmpB 制剂均未显示出针对 293T 细胞的细胞毒性。对于 THP1 细胞，只有 Fungizone (TM) 和 Ambisome (TM) 在 500 μg/L 时表现出细胞毒性（n = 4-10，p < 0.05）。计算出的不同制剂对白色念珠菌的 EC50 如下：iCo-010 为 26.8 +/- 2.9，iCo-009 为 74.6 +/- 8.9，Ambisome (TM) 为 109 +/- 31，Fungizone (TM) 为 87.1 +/- 22（μg AmpB/L，n = 6-12，p < 0.05).结论：AmpB 配方 分析对 293T 细胞没有细胞毒性。在 Fungizone (TM) 和 Ambisome (TM) 中观察到 THP1 细胞的细胞毒性，但新型 AmpB 制剂则没有。与其他三种 AmpB 制剂相比，iCo-010 在白色念珠菌模型中具有更高的功效。与 Fungizone (TM) 和 Ambisome (TM) 相比，iCo-010 不存在细胞毒性，并且对念珠菌模型具有更高的功效，表明 iCo-010 具有治疗念珠菌病的潜力。
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 (TM) a commercial AmpB formulation.The purpose of this study was to determine the cytotoxicity of Fungizone (TM), Ambisome (TM) 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 (TM) and Ambisome (TM) showed cytotoxicity at 500 mu g/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 (TM) and 87.1 +/- 22 for Fungizone (TM) (mu g 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 (TM) and Ambisome (TM), 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 (TM) and Ambisome (TM) suggest that iCo-010 has potential in treating candidiasis.