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

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.

journal_name

Int J Nanomedicine

journal_title

International journal of nanomedicine

authors

Ribeiro TG,Chávez-Fumagalli MA,Valadares DG,França JR,Rodrigues LB,Duarte MC,Lage PS,Andrade PH,Lage DP,Arruda LV,Abánades DR,Costa LE,Martins VT,Tavares CA,Castilho RO,Coelho EA,Faraco AA

doi

10.2147/IJN.S55678

subject

Has Abstract

pub_date

2014-02-14 00:00:00

pages

877-90

eissn

1176-9114

issn

1178-2013

pii

ijn-9-877

journal_volume

pub_type

杂志文章

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