Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes.
Vijay Kumar Prajapati,Kalpana Awasthi,Shalini Gautam,Thakur Prasad Yadav,Madhukar Rai,O.N. Srivastava,Shyam Sundar +6 more
TLDR
The results of these experiments clearly demonstrate that f-CNT-AmB has significantly greater antileishmanial efficacy than AmB and had no significant cytotoxic effects.Abstract:
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 mg/mL; 7.31+1.16 mg/mL; 0.66+0.17 mg/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 mg/mL versus 0.03263+0.00123 mg/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%; P¼0.0004). 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.read more
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