Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary...

Area of Science:

• Pharmacology and Drug Delivery
• Mycology and Infectious Diseases
• Toxicology

Background:

• Amphotericin B (AMB) is a critical antifungal agent, but its use is limited by toxicity.
• Liposomal formulations improve AMB safety but can be costly.
• Novel formulations are needed to optimize AMB delivery and reduce side effects.

Purpose of the Study:

• To characterize a new micellar formulation of amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5).
• To compare the biodistribution, nephrotoxicity, and efficacy of AMB:DCH 1:1.5 against pulmonary aspergillosis with a liposomal AMB formulation.
• To evaluate the therapeutic potential of AMB:DCH 1:1.5.

Main Methods:

• Preparation and characterization of AMB:DCH 1:1.5 micellar formulation.
• Intravenous administration of AMB:DCH 1:1.5 and liposomal AMB in a murine model of pulmonary aspergillosis.
• Assessment of drug biodistribution (lung and kidney concentrations), nephrotoxicity, and survival rates.
• Fungal burden reduction analysis.

Main Results:

• AMB:DCH 1:1.5 achieved 2.8-fold higher lung concentrations and significantly lower kidney exposure compared to liposomal AMB.
• Both formulations demonstrated similar efficacy in terms of survival percentages and fungal burden reduction.
• AMB:DCH 1:1.5 exhibited slightly lower nephrotoxicity than the liposomal formulation.

Conclusions:

• The AMB:DCH 1:1.5 micellar formulation exhibits a favorable biodistribution profile with enhanced lung targeting and reduced kidney accumulation.
• This formulation shows comparable efficacy and potentially reduced toxicity compared to liposomal amphotericin B.
• AMB:DCH 1:1.5 represents a promising alternative for treating pulmonary aspergillosis.