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

Authors Burgess BL, He Y, Baker MM, Luo B, Carroll SF, Forte TM, Oda MN

Received 18 June 2013

Accepted for publication 30 August 2013

Published 12 December 2013 Volume 2013:8(1) Pages 4733—4743

DOI https://doi.org/10.2147/IJN.S50113

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Braydon L Burgess,1,2 Yumin He,1 Mandie M Baker,1,2 Bing Luo,2 Stephen F Carroll,2 Trudy M Forte,2 Michael N Oda1

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

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: nanoparticles, infectious diseases, drug delivery, candidiasis, apolipoprotein A-I

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