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Toxicity of amphotericin B emulsion to cultured canine kidney cell monolayers
K A Lamb1, C Washington, S S Davis
1Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
Abstract:
The effect of amphotericin B in an emulsion formulation on the integrity of monolayers of kidney cells has been studied. Whereas a conventional solubilized amphotericin formulation (Fungizone, Squibb) caused a loss in monolayer integrity at concentrations above 1 microgram mL-1, the emulsion formulation had no measurable effect on confluence at amphotericin concentrations up to 100 micrograms mL-1. The emulsion retained a comparable antifungal activity to that of Fungizone against Saccharomyces cerevisiae in suspension culture. These results parallel the observed erythrocyte lysis data obtained previously using amphotericin B emulsions, and suggest that the emulsion formulation may have a lower toxicity and improved therapeutic potential over existing formulations.
Insights
A novel amphotericin B emulsion formulation shows significantly reduced kidney cell toxicity compared to conventional formulations. This improved formulation maintains antifungal efficacy while potentially offering enhanced therapeutic benefits.
Area of Science:
- Pharmacology
- Cell Biology
- Drug Delivery
Background:
- Amphotericin B is a critical antifungal agent but exhibits significant nephrotoxicity.
- Conventional formulations often require solubilizing agents that can contribute to toxicity.
- Improving the safety profile of amphotericin B is crucial for its clinical application.
Purpose of the Study:
- To evaluate the impact of an amphotericin B emulsion formulation on kidney cell monolayer integrity.
- To compare the toxicity and antifungal activity of the emulsion formulation against a conventional formulation.
- To assess the potential of the emulsion for reduced toxicity and improved therapeutic outcomes.
Main Methods:
- Monolayer integrity of kidney cells was assessed using a standard cell culture model.
- Cell confluence was measured to quantify the effect of different amphotericin B formulations.
- Antifungal activity was determined against Saccharomyces cerevisiae in suspension culture.
Main Results:
- The amphotericin B emulsion formulation demonstrated no measurable effect on kidney cell monolayer confluence at concentrations up to 100 µg/mL.
- Conventional amphotericin B formulations caused a loss of monolayer integrity at concentrations above 1 µg/mL.
- The emulsion formulation exhibited comparable antifungal activity to the conventional formulation.
Conclusions:
- The amphotericin B emulsion formulation exhibits significantly lower toxicity to kidney cells compared to conventional solubilized formulations.
- The emulsion formulation retains potent antifungal activity, suggesting a favorable therapeutic index.
- These findings indicate that amphotericin B emulsions may offer an improved safety and efficacy profile for treating fungal infections.