Title
Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Berlin ,
Subject
Biology
Human medicine
Source (journal)
Mycoses: diagnosis, therapy and prophylaxis of fungal diseases. - Berlin
Volume/pages
58(2015) :3 , p. 127-132
ISSN
0933-7407
ISI
000349951800002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Invasive aspergillosis (IA) has become increasingly common and is characterised by high morbidity and mortality. Upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. This laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC, miltefosine, posaconazole and voriconazole were determined for Aspergillus fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long-term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity against A. fumigatus (IC50 = 1.04 lmol l 1). Intraperitoneal administration of 50 mg kg 1 day 1 OlPC significantly reduced the fungal organ burdens at 4 days post-infection (dpi). Although 5- and 10-day OlPC treatment improved survival, organ burdens were not affected at 10 and 15 dpi. While this study showed excellent in vitro activity of OlPC against Aspergillus spp., its therapeutic efficacy in an acute mouse model for IA was less convincing. Given the limited therapeutic options in the current antifungal market for invasive infections, OlPC activity should be assessed in a less stringent in vivo model, potentially in combination treatment with other already marketed antifungal drugs.
E-info
https://repository.uantwerpen.be/docman/iruaauth/d072a2/643f9447443.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/386f6c/9880.pdf
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