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

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. A mannose-anchored t...

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Bibliographic Details
Published in:Nanomedicine (London, England) England), 2017-01, Vol.12 (2), p.99-115
Main Authors: Shahnaz, Gul, Edagwa, Benson J, McMillan, JoEllyn, Akhtar, Sohail, Raza, Abida, Qureshi, Naveeda A, Yasinzai, Masoom, Gendelman, Howard E
Format: Article
Language:English
Subjects:
Acids
amphotericin B
Amphotericin B - chemistry
Amphotericin B - therapeutic use
Animals
Antifungal agents
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - therapeutic use
Bioavailability
Biocompatibility
Cell Line
Chemotherapy
Chitosan - chemistry
Drug delivery systems
Drug resistance
Experiments
Humans
Infections
Leishmania donovani - drug effects
Leishmaniasis, Visceral - drug therapy
macrophage nanoparticle targeting
Macrophages - drug effects
Macrophages - parasitology
Mannose - chemistry
mannose receptors
Mice
Nanoparticles
NMR
Nuclear magnetic resonance
Parasites
Parasitic diseases
Peptides
Polymers
Retention
Scanning electron microscopy
Spectrum analysis
Systems stability
thiolated chitosan
visceral leishmaniasis
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Summary: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. A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. 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 IC for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. These studies show that MTC can serve as a platform for clearance of in macrophages.
ISSN:1743-5889
1748-6963
DOI:10.2217/nnm-2016-0325