Efficacy of Oral Encochleated Amphotericin B in a Mouse Model of Cryptococcal Meningoencephalitis
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Cryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.
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Encochleated amphotericin B was equally efficacious as amphotericin B and superior to oral fluconazole in cryptococcal meningoencephalitis.
“CAmB was found to be equally efficacious as AmB with superiority over oral fluconazole in cryptococcal meningoencephalitis [77].”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [77]
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- Authors
- Lu, R., Hollingsworth, C., Qiu, J., Wang, A., Hughes, E., Xin, X., Konrath, K. M., Elsegeiny, W., Park, Y.-D., Atakulu, L., Craft, J. C., Tramont, E. C., Mannino, R., & Williamson, P. R.
- Affiliations
- Jupiter (United States) (US)
- National Institutes of Health (US)
- National Center for Advancing Translational Sciences (US)
- Corresponding author
- Williamson, P. R.
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2019-06-25
- Volume
- 10
- Issue
- 3
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC6538785
- OpenAlex
- W2944902246
- Cited by
- 67
- References
- 37
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 12 · 2023: 9 · 2022: 12 · 2021: 14 · 2020: 9
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Matinas Biopharma
- HHS | NIH | National Institute of Allergy and Infectious Diseases (AI001123)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- cryptococcal meningoencephalitis, amphotericin B, oral drug delivery, nanoparticle encapsulation, 5-fluorocytosine, combination antifungal therapy, oral bioavailability, drug toxicity reduction, cryptococcal meningitis, HIV-associated cryptococcosis, mouse model
- MeSH terms
- Administration, Oral, Amphotericin B, Animals, Antifungal Agents, Cryptococcosis, Cryptococcus neoformans, Deoxycholic Acid, Disease Models, Animal, Drug Combinations, Drug Compounding, Drug Therapy, Combination, Female, Flucytosine, Lipids, Male, Meningoencephalitis, Rats, Sprague-Dawley, Mice, Rats, Nanoparticles
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