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Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™

Italia, Jagdishbhai L and Sharp, Andrew and Carter, Katharine C and Warn, Peter and Kumar, M N V Ravi (2011) Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™. PLoS One, 6 (10). e25744.

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Abstract

Background: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Methodology: Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113±20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. Conclusions: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™and responds only modestly to AmBisome®.

Item type: Article
ID code: 36463
Keywords: polymer nanoparticles, antifungal activity , amphotericin B polymer nanoparticles, Therapeutics. Pharmacology, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Medicine(all)
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Technology and Innovation Centre > Bionanotechnology
Depositing user: Pure Administrator
Date Deposited: 16 Dec 2011 05:21
Last modified: 15 Apr 2015 11:01
Related URLs:
URI: http://strathprints.strath.ac.uk/id/eprint/36463

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