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

2014; Dove Medical Press; Linguagem: Inglês

10.2147/ijn.s55678

1178-2013

Eduardo Antônio Ferraz Coelho, Tatiana Ribeiro, Miguel Á. Chávez‐Fumagalli, Diogo G. Valadares, Juçara Ribeiro Franca, Lívia dos Santos Rodrigues, Mariana Duarte, Paula S. Lage, Pedro José de Oliveira Andrade, Daniela P. Lage, Leonardo Vicentini Arruda, Daniel R. Abánades, Lourena E. Costa, Vívian T. Martins, Carlos J. Tavares, Rachel Oliveira Castilho, André Augusto Gomes Faraco,

Food Allergy and Anaphylaxis Research

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 .