Related Experiment Video
Updated: Aug 12, 2026
Gramicidin-based Fluorescence Assay; for Determining Small Molecules Potential for Modifying Lipid Bilayer Properties
Published on: October 13, 2010
In Vitro and In Vivo Study of Amphotericin B Formulation with Quaternized Bioreducible Lipidoids
Fang Liu1,2, Liu Yang1, Yamin Li1
1Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States.
Abstract:
Invasive fungal infections are well-known causes of morbidity and mortality in immunocompromised patients. Amphotericin B (AmB) is a polyene fungicidal agent with excellent properties of the broad antifungal spectrum, high activity, and relatively rare drug resistance. However, significant toxicities limit the clinical application of AmB and its conventional formulation AmB deoxycholate (Fungizone). Here we investigated nanoparticle formulations of AmB using synthetic biodegradable lipidoids and evaluated their stability, in vitro antifungal efficacy, and in vivo toxicity and pharmacokinetics. We found that the AmB formulated using a mixture of quaternized lipidoid (Q78-O14B) and DSPE-PEG2000 has the size around 70-100 nm and is stable during storage. The formulation showed no hemotoxicity to red blood cells (RBCs) in vitro. It also possesses the highest antifungal activity (in vitro) and lowest toxicity (both in vitro and in vivo). These metrics are significantly superior to the commercial antifungal product Fungizone. Meanwhile, AmB/Q78-O14B-P exhibited prolonged blood circulation in comparison to Fungizone in vivo. In AmB/Q78-O14B-P formulation, AmB was still detectable in the liver, spleen, and lung tissues with a concentration above the minimum inhibitory concentrations 72 h after low-dose intravenous injection. Based on these results, AmB in lipidoid nanoparticle formulation may produce sustained antifungal activity against blood-borne and systemic organ infections. Moreover, the new AmB formulation showed low nephrotoxicity and hepatotoxicity in rats even at high doses, allowing a dramatically wider and safer therapeutic window than Fungizone. This method provides a means to develop much needed antifungal agents that will be more therapeutically efficacious, more affordable (than AmBisome), and less toxic (than Fungizone) for the treatment of systemic fungal infections.
Insights
A novel nanoparticle formulation of Amphotericin B (AmB) using lipidoids demonstrates superior antifungal efficacy and reduced toxicity compared to conventional treatments. This innovation offers a safer, more effective option for invasive fungal infections.
Area of Science:
- Nanotechnology
- Pharmaceutical Sciences
- Mycology
Background:
- Invasive fungal infections pose significant risks, particularly for immunocompromised individuals.
- Amphotericin B (AmB) is a potent antifungal but limited by toxicity in its conventional formulation (Fungizone).
- Need for safer and more effective antifungal therapies is critical.
Purpose of the Study:
- To develop and evaluate a novel nanoparticle formulation of Amphotericin B (AmB) using synthetic biodegradable lipidoids.
- To assess the stability, in vitro antifungal efficacy, in vivo toxicity, and pharmacokinetic profile of the new AmB formulation.
- To compare the new formulation against the commercial Fungizone.
Main Methods:
- Formulation of AmB using a mixture of quaternized lipidoid (Q78-O14B) and DSPE-PEG2000.
- Evaluation of nanoparticle size, stability during storage.
- In vitro antifungal activity and hemotoxicity assays.
- In vivo toxicity, pharmacokinetic studies, and tissue distribution in rats.
- Comparison with Amphotericin B deoxycholate (Fungizone).
Main Results:
- The AmB lipidoid nanoparticle formulation (AmB/Q78-O14B-P) exhibited optimal size (70-100 nm) and storage stability.
- Demonstrated superior in vitro antifungal activity and significantly lower in vitro and in vivo toxicity, including reduced nephrotoxicity and hepatotoxicity.
- Showed prolonged blood circulation and sustained drug levels in organs (liver, spleen, lung) for up to 72 hours post-injection.
- Offered a wider and safer therapeutic window compared to Fungizone.
Conclusions:
- AmB formulated in lipidoid nanoparticles presents a promising strategy for sustained antifungal activity against systemic and blood-borne infections.
- This novel formulation offers enhanced therapeutic efficacy and safety, potentially overcoming the limitations of conventional Amphotericin B.
- The development provides a pathway for more effective, affordable, and less toxic antifungal agents for treating invasive fungal infections.
