A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model.
To develop an oral formulation of amphotericin B (AmB) that is stable at the temperatures of WHO Climatic Zones 3 and 4 (30-43 °C) and to evaluate its efficacy in a murine model of visceral leishmaniasis (VL).The stability testing of four novel oral lipid AmB formulations composed of mono- and di-gl...
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2010-12-01
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doaj-90b05b1ffe7d4b2b94e3d93d3a356b9e2020-11-25T01:32:48ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352010-12-01412e91310.1371/journal.pntd.0000913A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model.Ellen K WasanPavel GershkovichJinying ZhaoXiaohua ZhuKarl WerbovetzRichard R TidwellJohn G ClementSheila J ThorntonKishor M WasanTo develop an oral formulation of amphotericin B (AmB) that is stable at the temperatures of WHO Climatic Zones 3 and 4 (30-43 °C) and to evaluate its efficacy in a murine model of visceral leishmaniasis (VL).The stability testing of four novel oral lipid AmB formulations composed of mono- and di-glycerides and pegylated esters (iCo-010 to iCo-013) was performed over 60 d and analyzed by HPLC-UV. In addition, the four formulations were incubated 4 h in fasted-state simulated intestinal fluid. AmB concentration was measured spectrophotometrically and emulsion droplet diameter was assessed by dynamic light scattering. Antileishmanial activity of iCo-010 was evaluated at increasing oral doses (2.5 to 10 mg/kg) in a murine model of VL.AmB stability in the lipid formulation (iCo-010) was >75% over 60 days. After 4 h in fasted-state simulated intestinal fluid, AmB concentration was >95%. iCo-010 demonstrated significant efficacy when orally administered to VL-infected mice bid for five days (inhibition of 99%, 98%, and 83% at 10, 5 and 2.5 mg/kg compared to the vehicle control). In addition, the qd dose of 20 mg/kg provided 96% inhibition compared to the vehicle control.The oral AmB formulation iCo-010 is stable at the temperatures of WHO Climatic Zones 3 and 4 (30-43 °C). iCo-010 showed excellent antileishmanial activity at both 10 mg/kg po bid for 5 days (<99% reduction in parasitic infection) and 20 mg/kg po qd for 5 days (95% inhibition when compared to control).http://europepmc.org/articles/PMC2998436?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ellen K Wasan Pavel Gershkovich Jinying Zhao Xiaohua Zhu Karl Werbovetz Richard R Tidwell John G Clement Sheila J Thornton Kishor M Wasan |
spellingShingle |
Ellen K Wasan Pavel Gershkovich Jinying Zhao Xiaohua Zhu Karl Werbovetz Richard R Tidwell John G Clement Sheila J Thornton Kishor M Wasan A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. PLoS Neglected Tropical Diseases |
author_facet |
Ellen K Wasan Pavel Gershkovich Jinying Zhao Xiaohua Zhu Karl Werbovetz Richard R Tidwell John G Clement Sheila J Thornton Kishor M Wasan |
author_sort |
Ellen K Wasan |
title |
A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. |
title_short |
A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. |
title_full |
A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. |
title_fullStr |
A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. |
title_full_unstemmed |
A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral Leishmaniasis in a murine model. |
title_sort |
novel tropically stable oral amphotericin b formulation (ico-010) exhibits efficacy against visceral leishmaniasis in a murine model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2010-12-01 |
description |
To develop an oral formulation of amphotericin B (AmB) that is stable at the temperatures of WHO Climatic Zones 3 and 4 (30-43 °C) and to evaluate its efficacy in a murine model of visceral leishmaniasis (VL).The stability testing of four novel oral lipid AmB formulations composed of mono- and di-glycerides and pegylated esters (iCo-010 to iCo-013) was performed over 60 d and analyzed by HPLC-UV. In addition, the four formulations were incubated 4 h in fasted-state simulated intestinal fluid. AmB concentration was measured spectrophotometrically and emulsion droplet diameter was assessed by dynamic light scattering. Antileishmanial activity of iCo-010 was evaluated at increasing oral doses (2.5 to 10 mg/kg) in a murine model of VL.AmB stability in the lipid formulation (iCo-010) was >75% over 60 days. After 4 h in fasted-state simulated intestinal fluid, AmB concentration was >95%. iCo-010 demonstrated significant efficacy when orally administered to VL-infected mice bid for five days (inhibition of 99%, 98%, and 83% at 10, 5 and 2.5 mg/kg compared to the vehicle control). In addition, the qd dose of 20 mg/kg provided 96% inhibition compared to the vehicle control.The oral AmB formulation iCo-010 is stable at the temperatures of WHO Climatic Zones 3 and 4 (30-43 °C). iCo-010 showed excellent antileishmanial activity at both 10 mg/kg po bid for 5 days (<99% reduction in parasitic infection) and 20 mg/kg po qd for 5 days (95% inhibition when compared to control). |
url |
http://europepmc.org/articles/PMC2998436?pdf=render |
work_keys_str_mv |
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