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J Antimicrob Chemother. 2011 Apr;66(4):874-9. doi: 10.1093/jac/dkr002. Epub 2011 Feb 3.

Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes.

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  • 1Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.

Abstract

OBJECTIVES:

This study describes the antileishmanial efficacy of the novel drug formulation of amphotericin B (AmB) attached to functionalized carbon nanotubes (f-CNTs) and compares it with AmB.

METHODS:

f-CNTs were prepared in a two-step chemical carboxylation and amidation process. The AmB was then attached to make f-CNT-AmB and its construction was confirmed by Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). The cytotoxicity of the constructed compound, f-CNT-AmB, was assessed in vitro using the J774A.1 macrophage cell line and in vivo using healthy BALB/c mice. Antileishmanial activity of AmB and f-CNT-AmB was assessed in vitro using a macrophage (J774A.1 cell line) model of Leishmania donovani infection. Antileishmanial activity was assessed in vivo by comparing the parasite load of hamsters treated with a 5 day course of AmB, f-CNTs or f-CNT-AmB initiated at 30 days after infection with L. donovani parasites.

RESULTS:

The FTIR spectroscopy and TEM data demonstrate the successful attachment of AmB to f-CNTs. The in vitro cytotoxicity of AmB, f-CNTs and f-CNT-AmB was measured by the cytotoxic concentration required to kill 50% of the cells: 0.48±0.06 μg/mL; 7.31±1.16 μg/mL; 0.66±0.17 μg/mL, respectively, in the J774A.1 cell line. The in vivo toxicity assessment of the compounds in BALB/c mice revealed no hepatic or renal toxicity. Against intracellular amastigotes the in vitro antileishmanial efficacy of f-CNT-AmB was significantly higher than that of AmB (IC50 0.00234±0.00075 μg/mL versus 0.03263±0.00123 μg/mL; P≤0.0001). The percentage inhibition of amastigote replication in hamsters treated with f-CNT-AmB was significantly more than that with AmB (89.85%±2.93% versus 68.97%±1.84%; P=0.0004).

CONCLUSIONS:

The results of these experiments clearly demonstrate that f-CNT-AmB has significantly greater antileishmanial efficacy than AmB and had no significant cytotoxic effects.

PMID:
21393222
[PubMed - indexed for MEDLINE]
PMCID:
PMC3307040
Free PMC Article

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