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Cited by 85Inhalation and Respiratory Drug DeliveryAdvanced Drug Delivery SystemsDrug Solubulity and Delivery Systems

Single dose and multiple dose studies of itraconazole nanoparticles

Vaughn, Jason M., McConville, Jason T., Burgess, David, Peters, Jay I., Johnston, Keith P., Talbert, Robert L., Williams, Robert O.·2006·European Journal of Pharmaceutics and Biopharmaceutics
DOI 10.1016/j.ejpb.2006.01.006
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Abstract

The objective of this study was to determine and compare the lung and serum concentrations in mice following oral and pulmonary dosing of amorphous nanoparticulate itraconazole (ITZ) compositions as well as the Sporanox oral solution (itraconazole/Janssen). Second, the steady state partitioning of ITZ in lung tissue and circulatory compartments following repeated oral and pulmonary dosing was determined. The pulmonary formulation (ITZ-pulmonary) consisted of ITZ, polysorbate 80, and poloxamer 407 in a 1:0.75:0.75 ratio and the oral formulation (ITZ-oral) consisted of ITZ, PEG 8000, poloxamer 188, and sorbitan monooleate 80 in a 1:1:2:1 ratio. Mice were dosed every 12 h by nebulization with ITZ-pulmonary, or by oral gavage with ITZ-oral or Sporanox oral solution (n = 12 per study arm). ITZ-pulmonary achieved significantly greater (>10-fold) lung tissue concentrations compared to the Sporanox oral solution and ITZ-oral. There were no statistical differences between the two oral formulations. ITZ-pulmonary achieved significantly greater lung levels per unit serum concentration compared to the orally dosed ITZ compositions. High and sustained lung tissue concentrations were achieved via inhalation of an amorphous nanoparticulate ITZ-pulmonary composition while maintaining serum levels which are above the minimum lethal concentration (MLC) of Aspergillus fumigatus.

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  • In mouse studies, pulmonary delivery of amorphous itraconazole nanoparticles resulted in a tenfold higher drug concentration in the lungs compared with oral administration of its commercial formulation and the unformulated drug.

    “In mouse studies, pulmonary delivery of amorphous itraconazole nanoparticles resulted in a tenfold higher drug concentration in the lungs compared with oral administration of its commercial formulation (Sporanox) and the unformulated drug 31 .”

    From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [31]

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Authors
Vaughn, J. M., McConville, J. T., Burgess, D., Peters, J. I., Johnston, K. P., Talbert, R. L., & Williams, R. O.
Affiliations
  • The University of Texas at Austin (US)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
  • Peters, Jay I.
  • Talbert, Robert L.
  • Williams, Robert O.
ORCID
Venue
European Journal of Pharmaceutics and Biopharmaceutics
Publisher
Elsevier BV
Published
2006-06
Volume
63
Issue
2
Pages
95-102
ISSN
0939-6411 (ISSN-L)
DOI
10.1016/j.ejpb.2006.01.006
OpenAlex
W2129673742
Cited by
85
References
28
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 1 · 2013: 5 · 2012: 4
FWCI
7.07
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
itraconazole, nanoparticles, pulmonary drug delivery, oral drug delivery, lung tissue concentration, serum concentration, nebulization, amorphous drug formulation, antifungal agents, Aspergillus fumigatus, poloxamer, polysorbates, PEG 8000
MeSH terms
Administration, Oral, Animals, Antifungal Agents, Drug Administration Schedule, Lung, Male, Mice, Inbred ICR, Particle Size, Rats, Sprague-Dawley, Itraconazole, Nanotechnology, Mice, Rats

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