Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis

Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds. Mannosylated thiolated chitosan and mannosylated thiolated chitosan-polyethyleneimine g...

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Bibliographic Details
Published in:Nanomedicine (London, England) England), 2018-01, Vol.13 (1), p.25-41
Main Authors: Sarwar, Hafiz S, Ashraf, Sehreen, Akhtar, Sohail, Sohail, Muhammad F, Hussain, Syed Z, Rafay, Muhammad, Yasinzai, Masoom, Hussain, Irshad, Shahnaz, Gul
Format: Article
Language:English
Subjects:
Biomedical materials
Drug delivery systems
Enzymes
glucantime
Leishmaniasis
macrophage targeting
mannose receptors
meglumine antimoniate
nanomedicine
Nanoparticles
P-gp inhibition
Parasites
Parasitic diseases
polyethyleneimine
Polymers
Software
thiomers
trypanothione reductase
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Summary:Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds. Mannosylated thiolated chitosan and mannosylated thiolated chitosan-polyethyleneimine graft were synthesized and characterized. Meglumine antimoniate-loaded nanoparticles were prepared and evaluated for TR and P-gp efflux pump inhibition, biocompatibility, macrophage uptake and antileishmanial potential. Thiomers inhibited TR with Ki 2.021. The macrophage uptake was 33.7- and 18.9-fold higher with mannosylated thiolated chitosan-polyethyleneimine graft and mannosylated thiolated chitosan nanoparticles, respectively, as compared with the glucantime. Moreover, the antileishmanial activity showed 14.41- and 7.4-fold improved IC for M-T and M-TCS, respectively as compared with glucantime. These results encouraged the concept that TR and P-gp inhibition by the use of thiomers improves the therapeutic efficacy of antimonial drugs.
ISSN:1743-5889
1748-6963
DOI:10.2217/nnm-2017-0255