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Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Authors Ribeiro TG, Chávez-Fumagalli MA, Valadares DG, Franca JR, Rodrigues LB, Duarte MC, Lage PS, Andrade PHR, Lage DP, Arruda LV, Abánades DR, Costa LE, Martins VT, Tavares CAP, Castilho RO, Coelho EAF, Faraco AAG

Received 9 October 2013

Accepted for publication 6 December 2013

Published 14 February 2014 Volume 2014:9(1) Pages 877—890

DOI https://doi.org/10.2147/IJN.S55678

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Tatiana G Ribeiro,1 Miguel A Chávez-Fumagalli,2 Diogo G Valadares,3 Juçara R França,1 Lívia B Rodrigues,1 Mariana C Duarte,2 Paula S Lage,2 Pedro H R Andrade,4 Daniela P Lage,4 Leonardo V Arruda,5,6 Daniel R Abánades,5,6 Lourena E Costa,2 Vivian T Martins,3 Carlos AP Tavares,3 Rachel O Castilho,1,7,* Eduardo AF Coelho,2,4,* André AG Faraco1,7,*

1Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 3Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 4Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 5Programa de Pós-Graduação em Patologia Humana, Universidade Federal da Bahia, Salvador, Bahia, Brazil; 6Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil; 7Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

*These authors contributed equally to this work

Abstract: The study reported here aimed to develop an optimized nanoparticle delivery system for amphotericin B (AmpB) using a polyelectrolyte complexation technique. For this, two oppositely charged polymers presenting anti-leishmanial activity – chitosan (Cs) and chondroitin sulfate (ChS) – were used: Cs as a positively charged polymer and ChS as a negatively charged polymer. The chitosan (NQ) nanoparticles, chitosan-chondroitin sulfate (NQC) nanoparticles, and chitosan-chondroitin sulfate-amphotericin B (NQC-AmpB) nanoparticles presented a mean particle size of 79, 104, and 136 nm, respectively; and a polydispersity index of 0.2. The measured zeta potential of the nanoparticles indicated a positive charge in their surface, while scanning and transmission electron microscopy revealed spherical nanoparticles with a smooth surface. Attenuated total reflectance-Fourier transform infrared spectroscopy analysis showed an electrostatic interaction between the polymers, whereas the release profile of AmpB from the NQC-AmpB nanoparticles showed a controlled release. In addition, the Cs; ChS; and NQ, NQC, and NQC-AmpB nanoparticles proved to be effective against promastigotes of Leishmania amazonensis and Leishmania chagasi, with a synergistic effect observed between Cs and ChS. Moreover, the applied NQ, NQC, and NQC-AmpB compounds demonstrated low toxicity in murine macrophages, as well as null hemolytic activity in type O+ human red blood cells. Pure AmpB demonstrated high toxicity in the macrophages. The results show that cells infected with L. amazonensis and later treated with Cs, ChS, NQ, NQC, NQC-AmpB nanoparticles, or pure AmpB presented with a significant reduction in parasite number in the order of 24%, 31%, 55%, 66%, 90%, and 89%, respectively. The data presented indicate that the engineered NQC-AmpB nanoparticles could potentially be used as an alternative therapy to treat leishmaniasis, mainly due its low toxicity to mammals' cells.

Keywords: chitosan, chondroitin, amphotericin B, nanoparticles, Leishmania spp.

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