Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

Gul Shahnaz; Benson J. Edagwa; Joellyn McMillan; Sohail Akhtar; Abida Raza; Naveeda A. Qureshi; Masoom Yasinzai; Howard E. Gendelman

doi:10.2217/nnm-2016-0325

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

Gul Shahnaz, Benson J. Edagwa, Joellyn McMillan, Sohail Akhtar, Abida Raza, Naveeda A. Qureshi, Masoom Yasinzai, Howard E. Gendelman

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC₅₀ for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

Original language	English (US)
Pages (from-to)	99-115
Number of pages	17
Journal	Nanomedicine
Volume	12
Issue number	2
DOIs	https://doi.org/10.2217/nnm-2016-0325
State	Published - Jan 2017

Keywords

amphotericin B
macrophage nanoparticle targeting
mannose receptors
thiolated chitosan
visceral leishmaniasis

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
General Materials Science
Development

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title = "Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis",

abstract = "Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.",

keywords = "amphotericin B, macrophage nanoparticle targeting, mannose receptors, thiolated chitosan, visceral leishmaniasis",

author = "Gul Shahnaz and Edagwa, {Benson J.} and Joellyn McMillan and Sohail Akhtar and Abida Raza and Qureshi, {Naveeda A.} and Masoom Yasinzai and Gendelman, {Howard E.}",

note = "Publisher Copyright: {\textcopyright} 2017 Benson Edagwa.",

year = "2017",

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doi = "10.2217/nnm-2016-0325",

language = "English (US)",

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AU - Shahnaz, Gul

AU - Edagwa, Benson J.

AU - McMillan, Joellyn

AU - Akhtar, Sohail

AU - Raza, Abida

AU - Qureshi, Naveeda A.

AU - Yasinzai, Masoom

AU - Gendelman, Howard E.

PY - 2017/1

Y1 - 2017/1

N2 - Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

AB - Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

KW - amphotericin B

KW - macrophage nanoparticle targeting

KW - mannose receptors

KW - thiolated chitosan

KW - visceral leishmaniasis

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Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

Abstract

Keywords

ASJC Scopus subject areas

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