{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T21:18:55Z","timestamp":1771017535533,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Pulmocide Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Although anti\u2010fungal triazoles are dosed orally or systemically for <jats:italic>Aspergillus fumigatus<\/jats:italic> infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in <jats:italic>A.\u00a0fumigatus<\/jats:italic> (itraconazole susceptible: <jats:styled-content style=\"fixed-case\">ATCC<\/jats:styled-content>13073 [Af]; or resistant: <jats:styled-content style=\"fixed-case\">NCPF<\/jats:styled-content>7100 [AfR]) infected, temporarily neutropenic A\/J mice. Once daily treatment produced a dose\u2010dependent improvement of survival of Af\u2010infected mice (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content><jats:sub>50<\/jats:sub>: 0.019\u00a0mg\/mouse [approx. 0.755\u00a0mg\/kg, in]), similar to its potency (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content><jats:sub>50<\/jats:sub>: 0.775\u00a0mg\/kg, po) after once daily oral dosing. For AfR infection, either intranasal or oral posaconazole was largely ineffective on survival, although the highest dose of intranasal treatment (0.35\u00a0mg\/mouse) achieved 75% survival rate. Early intervention (treated on days 0, 1, 2 and 3 postinfection) and late intervention (treated on days 1, 2 and 3) with intranasal posaconazole (0.014\u20100.35\u00a0mg\/mouse) demonstrated potent inhibition of lung fungal load and galactomannan levels in both bronchoalveolar lavage fluid (<jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content>) and serum as well as inflammatory cells, <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 and malondialdehyde (<jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content>. Thus, posaconazole when dosed intranasally once daily showed an improvement of survival equivalent to or better than oral treatment, and produced potent inhibition of fungal load and biomarkers.<\/jats:p>","DOI":"10.1111\/myc.12653","type":"journal-article","created":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T04:02:55Z","timestamp":1499832175000},"page":"728-735","source":"Crossref","is-referenced-by-count":5,"title":["Effects of intranasally dosed posaconazole on fungal load and biomarkers in <i>Aspergillus fumigatus<\/i> infected immunocompromised mice"],"prefix":"10.1111","volume":"60","author":[{"given":"Genki","family":"Kimura","sequence":"first","affiliation":[{"name":"Laboratory of Physiology and Anatomy Nihon University School of Pharmacy  Funabashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Nakaoki","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy Nihon University School of Pharmacy  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