Stearylamine-bearing cationic liposomes kill Leishmania parasites through surface exposed negatively charged phosphatidylserine.
OBJECTIVE
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.
Banerjee
Antara
A
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India.
Roychoudhury
Jayeeta
J
Ali
Nahid
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004339:Drug Compounding; D004563:Electrochemistry; D007893:Leishmania donovani / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010101:Oxygen Consumption / Q000187:drug effects; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D000588:Amines; D017304:Annexin A5; D000981:Antiprotozoal Agents; D008081:Liposomes; D010718:Phosphatidylserines; D000255:Adenosine Triphosphate; C009317:stearylamine