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JAC Advance Access published online on May 2, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn189
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Antileishmanial activity of nano-amphotericin B deoxycholate

Krishna Das Manandhar1, Thakur Prasad Yadav2, Vijay Kumar Prajapati1, Subodh Kumar1, Madhukar Rai1, Anuradha Dube3, Onkar Nath Srivastava2 and Shyam Sundar1,*

1 Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India 2 Department of Physics, Banaras Hindu University, Varanasi 221 005, India 3 Division of Parasitology, Central Drug Research Institute, Lucknow 226001, India

Received 8 December 2007; returned 28 January 2008; revised 27 March 2008; accepted 31 March 2008

* Corresponding author. Tel: +91-542-2367795; Fax: +91-542-2367568; E-mail: drshyamsundar{at}hotmail.com

Objectives: The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis.

Methods: We have formulated nanoparticles (10–20 nM) from amphotericin B deoxycholate (1–2 µM) by applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue burden in spleen were evaluated for nano-amphotericin B and conventional amphotericin B. Both nano-amphotericin B and conventional amphotericin B were injected intraperitoneally at 5 mg/kg per day for 5 days.

Results: The inhibition of amastigotes in the splenic tissue with nano-amphotericin B was significantly more than with conventional amphotericin B (92.18% versus 74.57%, P = 0.005). Similarly, the suppression of parasite replication in the spleen was also found to be significant (99.18% versus 97.17%, P = 0.05). In a cytotoxicity test, nano-amphotericin B against the J774A cell line had a CC50 of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED50.

Conclusions: Nanoparticles of amphotericin B had significantly greater efficacy than conventional amphotericin B. This formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to conventional amphotericin B.

Key Words: visceral leishmaniasis , Leishmania donovani , nanoparticles , nanomedicine , in vitro , in vivo


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