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Cited by 43Antifungal resistance and susceptibilityInhalation and Respiratory Drug DeliveryFungal Infections and Studies

Aerosolized nanostructured itraconazole as prophylaxis against invasive pulmonary aspergillosis

Alvarez, Carlos A., Wiederhold, Nathan P., McConville, Jason T., Peters, Jay I., Najvar, Laura K., Graybill, John R., Coalson, Jacqueline J., Talbert, Robert L. +4 more·2007·Journal of Infection
DOI 10.1016/j.jinf.2007.01.014
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Abstract

Objective Prophylactic strategies against invasive pulmonary aspergillosis are often limited by drug interactions and toxicities. Targeted airway delivery of antifungals to the lungs may avoid these pitfalls. We evaluated the effectiveness of an aerosolized nanostructured formulation of itraconazole produced by spray freezing into liquid (SFL) as prophylaxis against invasive pulmonary aspergillosis caused by A. fumigatus.Methods Immunocompromised Balb/C mice received either itraconazole by oral gavage (Sporanox Oral Liquid [SOL] 30 mg/kg TID) or by aerosolization (SFL 30 mg/kg via 20 min aerosolizations, or control, BID). Dosing began 2 days prior to pulmonary inoculation with A. fumigatus and continued for 7 days post-inoculation. Changes in lung histopathology were also assessed. In the survival arm, mice were monitored over a 5 day period following discontinuation of therapy and survival was assessed by Kaplan-Meier analysis.Results SFL survival (35%) was greater compared to control (10%; p=0.03) and SOL (0%; p=0.02). Histopathology demonstrated severe invasive disease involving vessels and small airways in control and SOL animals. SFL animals demonstrated colonization with some invasion predominately of large airways.Conclusions Prophylactic aerosolization of nanostructured SFL significantly improved survival and limited invasive disease of small airways due to A. fumigatus.

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Crossref · 10.1016/j.jinf.2007.01.014

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  • In a murine Aspergillus fumigatus infection model, pulmonary nanoparticle treatment increased median survival (7.5 days) compared with oral Sporanox treatment (5 days).

    “In a murine Aspergillus fumigatus infection model, the same group observed an increased median survival in the pulmonary nanoparticle treated group (7.5 days) compared with oral Sporanox treated group (5 days) 32 .”

    From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [32]

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Authors
Alvarez, C. A., Wiederhold, N. P., McConville, J. T., Peters, J. I., Najvar, L. K., Graybill, J. R., Coalson, J. J., Talbert, R. L., Burgess, D. S., Bocanegra, R., Johnston, K. P., & Williams, R. O.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • The University of Texas at Austin (US)
Corresponding author
Wiederhold, Nathan P.
ORCID
Venue
Journal of Infection
Publisher
Elsevier BV
Published
2007-07
Volume
55
Issue
1
Pages
68-74
ISSN
0163-4453 (ISSN-L)
DOI
10.1016/j.jinf.2007.01.014
OpenAlex
W2083961750
Cited by
43
References
40
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 4
FWCI
2.94
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Infection (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
itraconazole, aerosol drug delivery, invasive pulmonary aspergillosis, Aspergillus fumigatus, antifungal prophylaxis, immunodeficient mice, survival, lung histopathology
MeSH terms
Aerosols, Animals, Antifungal Agents, Aspergillosis, Aspergillus fumigatus, Disease Models, Animal, Female, Humans, Lung, Lung Diseases, Fungal, Mice, Inbred BALB C, Immunocompromised Host, Treatment Outcome, Itraconazole, Nanostructures, Mice

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