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JAC Advance Access published online on October 26, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm396
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© The Author 2007. 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

Stearylamine-bearing cationic liposomes kill Leishmania parasites through surface exposed negatively charged phosphatidylserine

Antara Banerjee{dagger}, Jayeeta Roychoudhury{dagger} and Nahid Ali*

Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India

Received 13 February 2007; returned 20 June 2007; revised 18 July 2007; accepted 24 September 2007

* Corresponding author. Tel: +91-33-2473-3491/6793/0492; Fax: +91-33-2473-0284/5197; E-mail: nali{at}iicb.res.in

Objectives: Lipid-associated formulations of antileishmanial agents have proved to be more effective therapies with reduced toxicities. Previous studies from our group and others revealed that liposomes bearing phosphatidylcholine and stearylamine (SA) themselves kill Leishmania and other protozoan parasites in vitro and in vivo, without causing any adverse effect on host. In the present study, we offer detailed insights into the mechanism of action of these liposomes.

Methods: Mechanism study was carried out using fluorometric, confocal and electron microscopic methods.

Results: Herein, we provide evidence for induction of membrane disruption by specific interaction with surface phosphatidylserine (PS) of Leishmania promastigotes and amastigotes, phospholipids normally not found on mammalian cell surface, with SA-containing liposomes. Cell surface PS on different forms of Leishmania facilitated liposome-induced parasite killing. The target selectivity of the liposomes was further proved through inhibition of antileishmanial activity with annexinV, and strong affinity with anionic PS rather than phosphatidic acid-containing liposomes for leishmanicidal activity.

Conclusions: SA-bearing liposomes specifically kill Leishmania, but are non-toxic to murine peritoneal macrophages and human erythrocytes.

Key Words: promastigotes , amastigotes , membrane , drug

{dagger} Both authors have contributed equally to this work.


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