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

被引：11

作者：

Leon, Carlos G. ^{[1
]}

Lee, Jinkyung ^{[1
]}

Bartlett, Karen ^{[2
]}

Gershkovich, Pavel ^{[1
]}

Wasan, Ellen K. ^{[3
]}

Zhao, Jinying ^{[1
]}

Clement, John G. ^{[4
]}

Wasan, Kishor M. ^{[1
]}

机构：

[1] Univ British Columbia, Fac Pharmaceut Sci, Div Pharmaceut & Biopharmaceut, Vancouver, BC V6T 1Z3, Canada

[2] Univ British Columbia, Fac Environm & Occupat Hlth, Vancouver, BC V6T 1Z3, Canada

[3] British Columbia Inst Technol, Sch Hlth Sci, Burnaby, BC V5G 3H2, Canada

[4] ICo Therapeut Inc, Vancouver, BC V6Z 1S4, Canada

来源：

LIPIDS IN HEALTH AND DISEASE | 2011年 / 10卷

基金：

加拿大健康研究院;

关键词：

Amphotericin B; Candida; cytotoxicity; monocytes; ANTIFUNGAL DRUG-RESISTANCE; VISCERAL LEISHMANIASIS; ASPERGILLUS-FUMIGATUS; FUNGAL-INFECTIONS; FLUCONAZOLE; UPDATE;

D O I：

10.1186/1476-511X-10-144

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：7