Engineering Telodendrimer Nanocarriers for Monomeric Amphotericin B Delivery

Area of Science:

• Nanotechnology
• Pharmacology
• Mycology

Background:

• Systemic fungal infections pose a growing global health threat.
• Amphotericin B (AmB) is a critical antifungal agent but exhibits dose-limiting toxicities, primarily nephrotoxicity.
• The therapeutic efficacy and toxicity of AmB are intrinsically linked to its aggregation state.

Purpose of the Study:

• To develop novel telodendrimer (TD) nanocarriers for Amphotericin B (AmB) encapsulation.
• To engineer nanocarrier core structures to control AmB aggregation status.
• To evaluate the impact of modulated AmB aggregation on antifungal activity, hemolytic properties, and cytotoxicity.

Main Methods:

• Synthesis of telodendrimer (TD) nanocarriers with tunable core structures.
• Encapsulation of Amphotericin B (AmB) within TD nanocarriers to control its aggregation state.
• Assessment of antifungal efficacy, hemolytic activity, and cytotoxicity of AmB-loaded nanocarriers in vitro and in vivo.

Main Results:

• Reduced aggregation of AmB within optimized TD nanocarriers correlated with enhanced antifungal activity.
• TD nanocarriers demonstrated attenuated hemolytic properties and reduced cytotoxicity to mammalian cells compared to free AmB.
• The optimized TD nanocarrier formulation significantly improved the therapeutic index and in vivo antifungal efficacy in a Candida albicans mouse infection model.

Conclusions:

• Telodendrimer (TD) nanocarriers offer a promising platform for developing safer and more effective Amphotericin B (AmB) formulations.
• Controlling AmB aggregation through nanocarrier design is a viable strategy to mitigate its toxicity while preserving antifungal potency.
• This approach represents a significant advancement over existing clinical AmB formulations like Fungizone and AmBisome.