Engineered Telodendrimer Nanocarriers for Monomeric Amphotericin B Delivery

Background:

Systemic fungal infections are an increasingly prevalent health problem. The hydrophobic polyene antibiotic Amphotericin B (AmB) is the drug of choice for these life-threatening invasive fungal infections. Unfortunately, it produces dose-limiting side effects such as nephrotoxicity. For example, Fungizone® is a conventional sodium deoxycholate micellar formulation of AmB that exhibits high nephrotoxicity and infusion-related reactions. Clinically approved liposomal formulations of AmB, such as AmBisome, reduces AmB toxicity, but do not offer better clinical efficacy. Numerous nanoformulations have been developed for AmB delivery to improve the efficacy and reduce toxicity and cost. However, current options cannot enable the fine-tuning of AmB aggregation in a nanocarrier, which is directly associated with the efficacy and toxicity of AmB formulation for clinical translation.

Technology Overview:

This technology is a PEGylated linear-dendritic telodendrimer (TD) nanocarrier platform for customized nanocarrier design. Different hydrophobic groups can be freely introduced on the dendritic periphery of TD to fine-tune the hydrophobicity and flexibility of the core structure of micelle to control AmB molecular aggregation. The AmB aggregation status in this nanoformulation has a positive correlation with the haemolytic activity and a reverse correlation with antifungal activity. The optimized nanoformulation, with the highest monomeric AmB, significantly improves the antifungal activities and reduces the toxicity both in vitro and in vivo in comparison to Fungizone and AmBisome. This offers significant promise for clinical translation with increased therapeutic window and reduced cost in comparison to the lipid formulations (e.g. AmBisome).

Advantages:

• Decreases toxicity compared to other AmB options.
• Increases clinical efficacy.
• Reduces cost.

Applications:

The primary application for this technology is the development of AmB therapeutics for the treatment of fungal infections.

Intellectual Property Summary:

Provisional Patent Application 63/441,993 filed on 1/30/2023

Stage of Development:

TRL 3 - Experimental proof of concept

Licensing Status:

This technology is available for licensing.

Licensing Potential:

This technology would be of interest to anyone involved in the development of treatments for fungal infections based on AmB, including:

• Pharmaceutical companies
• Medical research centers
• Hospitals
• Universities