Abstract

ObjectiveAn oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice.MethodsMice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain.ResultsAlthough the infection was relatively low (~ 60–100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group.ConclusionOral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

Highlights

  • Amphotericin B (AmB) is a polyene macrolide antibiotic used in the treatment of blood-borne fungal infections and parasitic infections

  • The carbon nanotubes were tested in a visceral leishmaniasis model in Syrian hamsters and showed high efficacy, the safety of carbon nanotubes in humans is still questionable [3]

  • The concentration of AmB in the tissues of the brain and liver were below the limit of quantification of the High performance liquid chromatography (HPLC) assay, in contrast; the highest concentrations of AmB were recovered from the kidneys and the spleen (Table 1)

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Summary

Results

The infection was relatively low (~ 60–100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group

Introduction
Results and discussion
Conclusions
Deray G
15. McMaster PD
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