Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis. (January 2018)

• Record Type: Journal Article
• Authors: Sarwar, Hafiz S; Ashraf, Sehreen; Akhtar, Sohail; Sohail, Muhammad F; Hussain, Syed Z; Rafay, Muhammad; Yasinzai, Masoom; Hussain, Irshad; Shahnaz, Gul
• Is Part Of: Nanomedicine. Volume 13:Number 1(2018)
• Page Start: 25
• Page End: 41
• Publication Date: 2018-01
• Subjects: glucantime -- Leishmaniasis -- macrophage targeting -- mannose receptors -- meglumine antimoniate -- nanomedicine -- P-gp inhibition -- polyethyleneimine -- thiomers -- trypanothione reductase; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2017-0255
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of Leishmania by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds.Methods: 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.Results: 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 in vitro antileishmanial activity showed 14.41- and 7.4-fold improved IC50 for M-T CS-g-PEI and M-TCS, respectively as compared with glucantime.Conclusion: These results encouraged the concept that TR and P-gp inhibition by the use of thiomers improves the therapeutic efficacy of antimonial drugs.