Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis

Nanomedicine : Nanotechnology, Biology, and Medicine
Khojasteh ShirkhaniSunil Shaunak

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. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The a...Continue Reading

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Citations

Jul 15, 2015·Biochemical and Biophysical Research Communications·Sunil Shaunak
Aug 27, 2016·Medical Mycology·Nir Osherov, Dimitrios P Kontoyiannis
Mar 28, 2018·Canadian Journal of Microbiology·David A SzalewskiRaúl G Barletta
Jun 1, 2017·Frontiers in Microbiology·Guillaume Desoubeaux, Carolyn Cray
Oct 6, 2020·Frontiers in Cellular and Infection Microbiology·Brenda KischkelCarlos P Taborda
Jan 19, 2021·Nano Research·Wenhao ZhongJun Wu
Oct 1, 2021·Mycopathologia·Darius Armstrong-James

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Methods Mentioned

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