Differential cytotoxicity of phospholipid analogues to pathogenic Acanthamoeba species and mammalian cells

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Abstract

Previous studies have reported the ability of several phospholipid analogues to successfully inhibit the growth of Acanthamoeba species in vitro. This study tests further phospholipid analogues, either as free drug or in liposomal formulations, and unlike previous studies, examines their comparative toxicities to mammalian cells.
The relative cytotoxic activities of the phospholipid derivatives hexadecyl-PC, octadecyl-PC, elaidyl-PC, erucyl-PC and edelfosine, against Acanthamoeba castellanii, Acanthamoeba polyphaga and a rabbit corneal epithelial (RCE) cell line, was determined by the alamarBlue (TM) assay. Free and liposomal formulations were compared for hexadecyl-PC and elaidyl-PC.
Both hexadecyl-PC and octadecyl-PC (IC50 values between 3.9 and 7.8 mu M) demonstrated considerable activity against A. castellanii, as did elaidyl-PC ( IC50 values between 15.6 and 31.25 mu M). Both hexadecyl-PC and elaidyl-PC also proved effective against A. polyphaga ( IC50 values between 15.6 and 31.25 and between 31.25 and 62.5 mu M, respectively). In contrast, neither erucyl-PC nor edelfosine was inhibitory against either Acanthamoeba species. The growth of RCE cells was inhibited by octadecyl-PC, erucyl-PC and edelfosine (octadecyl-PC and erucyl-PC IC50 values between 7.8 and 15.6 mu M and edelfosine IC50 values between 31.25 and 62.5 mu M). Liposomal formulations of hexadecyl-PC and elaidyl-PC were less effective than free drug against both Acanthamoeba species.
These results demonstrate that hexadecyl-PC has the highest therapeutic index and is the most promising for the treatment of acanthamoebiasis.

LanguageEnglish
Pages521-525
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume60
Issue number3
DOIs
Publication statusPublished - Sep 2007

Fingerprint

Acanthamoeba
Inhibitory Concentration 50
Phospholipids
Acanthamoeba castellanii
Epithelial Cells
Rabbits
Growth
Pharmaceutical Preparations
Cell Line
edelfosine

Keywords

  • APC
  • liposome
  • keratitis
  • leishmania-donovani
  • trypanosoma-cruzi
  • hexadecylphosohocholine miltefosine
  • opportunistic amebas
  • alkylphosphocolines
  • edelfosine
  • humans
  • brucei

Cite this

@article{59013cdbd6424df6b418ca84e09d4db1,
title = "Differential cytotoxicity of phospholipid analogues to pathogenic Acanthamoeba species and mammalian cells",
abstract = "Previous studies have reported the ability of several phospholipid analogues to successfully inhibit the growth of Acanthamoeba species in vitro. This study tests further phospholipid analogues, either as free drug or in liposomal formulations, and unlike previous studies, examines their comparative toxicities to mammalian cells. The relative cytotoxic activities of the phospholipid derivatives hexadecyl-PC, octadecyl-PC, elaidyl-PC, erucyl-PC and edelfosine, against Acanthamoeba castellanii, Acanthamoeba polyphaga and a rabbit corneal epithelial (RCE) cell line, was determined by the alamarBlue (TM) assay. Free and liposomal formulations were compared for hexadecyl-PC and elaidyl-PC. Both hexadecyl-PC and octadecyl-PC (IC50 values between 3.9 and 7.8 mu M) demonstrated considerable activity against A. castellanii, as did elaidyl-PC ( IC50 values between 15.6 and 31.25 mu M). Both hexadecyl-PC and elaidyl-PC also proved effective against A. polyphaga ( IC50 values between 15.6 and 31.25 and between 31.25 and 62.5 mu M, respectively). In contrast, neither erucyl-PC nor edelfosine was inhibitory against either Acanthamoeba species. The growth of RCE cells was inhibited by octadecyl-PC, erucyl-PC and edelfosine (octadecyl-PC and erucyl-PC IC50 values between 7.8 and 15.6 mu M and edelfosine IC50 values between 31.25 and 62.5 mu M). Liposomal formulations of hexadecyl-PC and elaidyl-PC were less effective than free drug against both Acanthamoeba species. These results demonstrate that hexadecyl-PC has the highest therapeutic index and is the most promising for the treatment of acanthamoebiasis.",
keywords = "APC, liposome, keratitis, leishmania-donovani, trypanosoma-cruzi, hexadecylphosohocholine miltefosine, opportunistic amebas, alkylphosphocolines, edelfosine, humans, brucei",
author = "James McBride and Mullen, {Alexander B.} and Carter, {K. Christine} and Roberts, {Craig W.}",
year = "2007",
month = "9",
doi = "10.1093/jac/dkm245",
language = "English",
volume = "60",
pages = "521--525",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
number = "3",

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TY - JOUR

T1 - Differential cytotoxicity of phospholipid analogues to pathogenic Acanthamoeba species and mammalian cells

AU - McBride, James

AU - Mullen, Alexander B.

AU - Carter, K. Christine

AU - Roberts, Craig W.

PY - 2007/9

Y1 - 2007/9

N2 - Previous studies have reported the ability of several phospholipid analogues to successfully inhibit the growth of Acanthamoeba species in vitro. This study tests further phospholipid analogues, either as free drug or in liposomal formulations, and unlike previous studies, examines their comparative toxicities to mammalian cells. The relative cytotoxic activities of the phospholipid derivatives hexadecyl-PC, octadecyl-PC, elaidyl-PC, erucyl-PC and edelfosine, against Acanthamoeba castellanii, Acanthamoeba polyphaga and a rabbit corneal epithelial (RCE) cell line, was determined by the alamarBlue (TM) assay. Free and liposomal formulations were compared for hexadecyl-PC and elaidyl-PC. Both hexadecyl-PC and octadecyl-PC (IC50 values between 3.9 and 7.8 mu M) demonstrated considerable activity against A. castellanii, as did elaidyl-PC ( IC50 values between 15.6 and 31.25 mu M). Both hexadecyl-PC and elaidyl-PC also proved effective against A. polyphaga ( IC50 values between 15.6 and 31.25 and between 31.25 and 62.5 mu M, respectively). In contrast, neither erucyl-PC nor edelfosine was inhibitory against either Acanthamoeba species. The growth of RCE cells was inhibited by octadecyl-PC, erucyl-PC and edelfosine (octadecyl-PC and erucyl-PC IC50 values between 7.8 and 15.6 mu M and edelfosine IC50 values between 31.25 and 62.5 mu M). Liposomal formulations of hexadecyl-PC and elaidyl-PC were less effective than free drug against both Acanthamoeba species. These results demonstrate that hexadecyl-PC has the highest therapeutic index and is the most promising for the treatment of acanthamoebiasis.

AB - Previous studies have reported the ability of several phospholipid analogues to successfully inhibit the growth of Acanthamoeba species in vitro. This study tests further phospholipid analogues, either as free drug or in liposomal formulations, and unlike previous studies, examines their comparative toxicities to mammalian cells. The relative cytotoxic activities of the phospholipid derivatives hexadecyl-PC, octadecyl-PC, elaidyl-PC, erucyl-PC and edelfosine, against Acanthamoeba castellanii, Acanthamoeba polyphaga and a rabbit corneal epithelial (RCE) cell line, was determined by the alamarBlue (TM) assay. Free and liposomal formulations were compared for hexadecyl-PC and elaidyl-PC. Both hexadecyl-PC and octadecyl-PC (IC50 values between 3.9 and 7.8 mu M) demonstrated considerable activity against A. castellanii, as did elaidyl-PC ( IC50 values between 15.6 and 31.25 mu M). Both hexadecyl-PC and elaidyl-PC also proved effective against A. polyphaga ( IC50 values between 15.6 and 31.25 and between 31.25 and 62.5 mu M, respectively). In contrast, neither erucyl-PC nor edelfosine was inhibitory against either Acanthamoeba species. The growth of RCE cells was inhibited by octadecyl-PC, erucyl-PC and edelfosine (octadecyl-PC and erucyl-PC IC50 values between 7.8 and 15.6 mu M and edelfosine IC50 values between 31.25 and 62.5 mu M). Liposomal formulations of hexadecyl-PC and elaidyl-PC were less effective than free drug against both Acanthamoeba species. These results demonstrate that hexadecyl-PC has the highest therapeutic index and is the most promising for the treatment of acanthamoebiasis.

KW - APC

KW - liposome

KW - keratitis

KW - leishmania-donovani

KW - trypanosoma-cruzi

KW - hexadecylphosohocholine miltefosine

KW - opportunistic amebas

KW - alkylphosphocolines

KW - edelfosine

KW - humans

KW - brucei

U2 - 10.1093/jac/dkm245

DO - 10.1093/jac/dkm245

M3 - Article

VL - 60

SP - 521

EP - 525

JO - Journal of Antimicrobial Chemotherapy

T2 - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 3

ER -