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Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles

Published online by Cambridge University Press:  04 May 2020

Ariane J. Sousa-Batista Open the ORCID record for Ariane J. Sousa-Batista [Opens in a new window] ,
Natalia Arruda-Costa ,
Douglas O. Escrivani ,
Franceline Reynaud ,
Patrick G. Steel  and
Bartira Rossi-Bergmann
Ariane J. Sousa-Batista*
Affiliation:
Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Nanotechnology Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering – COPPE, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Natalia Arruda-Costa
Affiliation:
Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Douglas O. Escrivani
Affiliation:
Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Franceline Reynaud
Affiliation:
Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Patrick G. Steel
Affiliation:
Department of Chemistry, Durham University, Durham, UK
Bartira Rossi-Bergmann
Affiliation:
Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
*
Author for correspondence: Ariane J. Sousa-Batista, E-mail: ariane@pent.coppe.ufrj.br
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Abstract

Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.

Keywords

Chalconechemotherapydrug delivery systemsLeishmanialocal treatment
Type
Research Article
Information
Parasitology , Volume 147 , Issue 9 , August 2020 , pp. 1032 - 1037
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

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