Related Experiment Video
Updated: Apr 16, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis
Khojasteh Shirkhani1, Ian Teo1, Darius Armstrong-James1
1Departments of Medicine, Infectious Diseases, Immunity and Chemistry, Imperial College London, Hammersmith campus, London, UK.
Abstract:
Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections.
From The Clinical Editor:
Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future.
Insights
New amphotericin B nanoparticles offer effective pre-exposure prophylaxis against Aspergillus fungal infections in transplant patients. This safe and cost-effective nanoparticle delivery to the lungs prevents invasive aspergillosis and reduces lung inflammation.
Area of Science:
- Mycology
- Nanotechnology
- Immunology
Background:
- Aspergillus species are life-threatening fungal pathogens, particularly in transplant patients, causing invasive aspergillosis with high mortality.
- Inhaled fungal spore germination leads to severe pneumonia, necessitating strategies like pre-exposure prophylaxis.
- Current treatment limitations drive the need for novel preventative approaches against invasive fungal infections.
Purpose of the Study:
- To develop and evaluate a novel, low molecular weight amphotericin B-polymethacrylic acid nanoparticle for preventing invasive aspergillosis.
- To assess the safety and efficacy of aerosolized nanoparticle delivery as a pre-exposure prophylaxis in a relevant preclinical model.
- To determine the impact of nanoparticle treatment on fungal burden and lung inflammation.
Main Methods:
- Synthesis of low molecular weight amphotericin B-polymethacrylic acid nanoparticles.
- In vitro toxicity assessment in lung epithelial cells and macrophages.
- In vivo efficacy study in an immunosuppressed mouse model of invasive aspergillosis using nebulizer-based prophylaxis.
- Quantification of Aspergillus burden and lung inflammatory markers (TNF-α).
Main Results:
- The developed nanoparticle was non-toxic in vitro and in vivo.
- Three days of nebulized nanoparticle prophylaxis effectively prevented fungal growth and lung inflammation in the mouse model.
- Treatment led to >99% killing of Aspergillus and a 90% reduction in lung TNF-α.
- Successful delivery of nanoparticles to the lungs via aerosolization was confirmed.
Conclusions:
- This study demonstrates in-vivo proof-of-principle for aerosolized amphotericin B nanoparticles as a safe and effective pre-exposure prophylaxis against invasive aspergillosis.
- The simple, cost-effective nanoparticle formulation and delivery method show promise for preventing fungal infections in immunocompromised individuals.
- These findings provide a strong foundation for advancing this nanoparticle-based strategy towards clinical trials.
More Related Videos
Related Concept Videos
01:15Antifungal Agents
01:25Transmission-based Precautions II: Airborne and Protective Environment
Airborne precautions:
Use airborne precautions when treating patients known or suspected to have diseases that spread through the air—for example, tuberculosis or measles. These organisms are present in smaller droplets expelled by an infected person and...