In Vitro Toxicity Of Caspofungin And Amphotericin B On Cells Of Epithelial Origin

Abstract

Abstract: : Purpose: Caspofungin is the first approved drug of a new class of anti-fungal agents called echinocandins, which inhibit fungal cell wall glucan synthesis. In view of its potential usage in topical treatment of fungal keratitis we tested the toxicity of caspofungin on two standardized cell lines of epithelial origin and compared it to amphotericin B. Method: Confluent monolayers of Vero and Chang cells were incubated with various concentrations (0.0001-1.5 mg/ml) of caspofungin or amphotericin B. Acute toxicity (up to 3 hours) was assessed by monitoring the permeability of cells to propidium iodide; chronic toxicity (7 days) was determined by monitoring the effect of the two drugs on esterase activity and cell proliferation. The viability of cells was also assessed by microscopic inspection. Results: Signs of acute toxicity became manifest at caspofungin concentrations ≥0.3 mg/ml in both Chang and Vero cells after one hour incubation. Chronic toxicity was observed at the same concentration in both cell types. In amphotericin B treated cells acute and chronic toxicity including degenerative morphological changes became evident at concentrations ≥0.005 mg/ml in both cell lines. Conclusions: Amphotericin B elicited toxicity well below the clinically tolerated topical standard concentration of 1.5 mg/ml. Caspofungin might be an interesting alternative broad-spectrum agent with reduced topical toxicity. Its effectiveness in vivo should be studied.

Keywords: 390 drug toxicity/drug effects • 414 fungal disease • 494 ocular irritancy/toxicity testing