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Activity of chitosan and its derivatives against Leishmania major and L. mexicana in vitro

Riezk, A; Raynes, JG; Yardley, V; Murdan, S; Croft, SL; (2019) Activity of chitosan and its derivatives against Leishmania major and L. mexicana in vitro. Antimicrobial Agents and Chemotherapy 10.1128/AAC.01772-19. (In press). Green open access

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Abstract

There is an urgent need for safe, efficacious, affordable and field-adapted drugs for the treatment of cutaneous leishmaniasis which affects around 1.5 million new people worldwide annually. Chitosan, a biodegradable cationic polysaccharide, has previously been reported to have antimicrobial, anti-leishmanial and immunostimulatory activities. We investigated the in vitro activity of chitosan and several of its derivatives and showed that pH of the culture medium plays a critical role on anti-leishmanial activity of chitosan against both extracellular promastigotes and intracellular amastigotes of Leishmania major and Leishmania mexicana Chitosan and its derivatives were approximately 7-20 times more active at pH 6.5 than at pH 7.5 with high molecular weight chitosan being the most potent. High molecular weight chitosan stimulated the production of nitric oxide and reactive oxygen species by uninfected and Leishmania infected macrophages in a time and dose dependent manner at pH 6.5. Despite the in vitro activation of bone marrow macrophages by chitosan to produce nitric oxide and reactive oxygen species, we showed that the anti-leishmanial activity of chitosan was not mediated by these metabolites. Finally, we showed that rhodamine-labelled chitosan is taken up by pinocytosis and accumulates in the parasitophorous vacuole of Leishmania infected macrophages.

Type: Article
Title: Activity of chitosan and its derivatives against Leishmania major and L. mexicana in vitro
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/AAC.01772-19
Publisher version: https://doi.org/10.1128/AAC.01772-19
Language: English
Additional information: © 2019 Riezk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Keywords: Cutaneous leishmaniasis, Leishmania major, Leishmania mexicana, chitosan, macrophage uptake
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10089182
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