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Int J Nanomedicine. 2013;8:4733-43. doi: 10.2147/IJN.S50113. Epub 2013 Dec 12.

NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency.

Author information

1
Children's Hospital Oakland Research Institute, Oakland, CA, USA ; Lypro Biosciences, Berkeley, CA, USA.
2
Children's Hospital Oakland Research Institute, Oakland, CA, USA.
3
Lypro Biosciences, Berkeley, CA, USA.

Abstract

OBJECTIVES:

NanoDisk-amphotericin B (ND-AMB) is a protein-phospholipid bioparticle containing a "super aggregate" form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB), are safer than the deoxycholate (DOC) solubilized form (DOC-AMB), the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious.

METHODS:

Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection.

RESULTS:

ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans, ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB.

CONCLUSION:

These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.

KEYWORDS:

apolipoprotein A-I; candidiasis; drug delivery; infectious diseases; nanoparticles

PMID:
24379661
PMCID:
PMC3867322
DOI:
10.2147/IJN.S50113
[Indexed for MEDLINE]
Free PMC Article

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