Variability in polyene content and cellular toxicity among deoxycholate amphotericin B formulations

Area of Science:

• Pharmacology
• Toxicology
• Infectious Diseases

Background:

• Amphotericin B is a critical antifungal agent.
• Variability in clinical efficacy and toxicity of amphotericin B formulations has been observed.
• Understanding formulation-specific toxicity is crucial for patient safety.

Purpose of the Study:

• To evaluate the in vitro toxicity of different amphotericin B deoxycholate formulations.
• To identify potential factors contributing to toxicity variations.

Main Methods:

• In vitro experiment using human mononuclear THP-1 cells.
• Exposure to various amphotericin B deoxycholate formulations at specified concentrations.
• Assessment of toxicity via interleukin (IL)-1beta expression.
• Quantification of amphotericin B content using ELISA and spectrophotometry.
• Evaluation of endotoxin contamination.

Main Results:

• Significant differences in IL-1beta expression (a marker of toxicity) were observed among formulations.
• Formulations from Sigma, Pharmacia, and Pharma-Tek showed increased IL-1beta expression.
• Amphotericin B content varied considerably between formulations, not fully explained by spectrophotometric analysis.
• Endotoxin contamination was assessed across all reagents.

Conclusions:

• The in vitro study confirms significant toxicity differences among amphotericin B deoxycholate formulations.
• Variability in pyrogenic toxins or other polyenes is the likely cause of observed toxicity differences.
• These findings highlight the importance of formulation quality control in antifungal therapy.