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PLoS One. 2011;6(10):e25744. doi: 10.1371/journal.pone.0025744. Epub 2011 Oct 6.

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

Author information

1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.

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®.

PMID:
21998690
PMCID:
PMC3188565
DOI:
10.1371/journal.pone.0025744
[Indexed for MEDLINE]
Free PMC Article

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