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

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 Oda11Children's Hospital Oakland Research Institute, Oakland, CA, USA; 2Lypro Biosciences, Berkeley, CA, USAObjectives: NanoDisk–amphotericin B (ND-AMB) is a protein-phosph...

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Autores principales:	Burgess BL, He Y, Baker MM, Luo B, Carroll SF, Forte TM, Oda MN
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/810fa6d6859543acb3aba2f432c93b26
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spelling	oai:doaj.org-article:810fa6d6859543acb3aba2f432c93b262021-12-02T00:39:11ZNanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency1178-2013https://doaj.org/article/810fa6d6859543acb3aba2f432c93b262013-12-01T00:00:00Zhttp://www.dovepress.com/nanodisk-containing-super-aggregated-amphotericin-b-a-high-therapeutic-a15274https://doaj.org/toc/1178-2013 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 Oda11Children's Hospital Oakland Research Institute, Oakland, CA, USA; 2Lypro Biosciences, Berkeley, CA, USAObjectives: 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-IBurgess BLHe YBaker MMLuo BCarroll SFForte TMOda MNDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 4733-4743 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Burgess BL He Y Baker MM Luo B Carroll SF Forte TM Oda MN NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
description	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 Oda11Children's Hospital Oakland Research Institute, Oakland, CA, USA; 2Lypro Biosciences, Berkeley, CA, USAObjectives: 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
format	article
author	Burgess BL He Y Baker MM Luo B Carroll SF Forte TM Oda MN
author_facet	Burgess BL He Y Baker MM Luo B Carroll SF Forte TM Oda MN
author_sort	Burgess BL
title	NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
title_short	NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
title_full	NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
title_fullStr	NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
title_full_unstemmed	NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency
title_sort	nanodisk containing super aggregated amphotericin b: a high therapeutic index antifungal formulation with enhanced potency
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/810fa6d6859543acb3aba2f432c93b26
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NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency

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