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JAC Advance Access published online on July 10, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm245
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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

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

James McBride, Alexander B. Mullen, K. Christine Carter and Craig W. Roberts*

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, Scotland, UK

Received 6 February 2007; returned 18 March 2007; revised 1 June 2007; accepted 12 June 2007

* Corresponding author. Tel/Fax: +44-141-548-4823; E-mail: c.w.roberts{at}strath.ac.uk

Objectives: 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.

Methods: 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 alamarBlueTMTM assay. Free and liposomal formulations were compared for hexadecyl-PC and elaidyl-PC.

Results: Both hexadecyl-PC and octadecyl-PC (IC50 values between 3.9 and 7.8 µM) demonstrated considerable activity against A. castellanii, as did elaidyl-PC (IC50 values between 15.6 and 31.25 µM). 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 µM, 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 µM and edelfosine IC50 values between 31.25 and 62.5 µM). Liposomal formulations of hexadecyl-PC and elaidyl-PC were less effective than free drug against both Acanthamoeba species.

Conclusions: These results demonstrate that hexadecyl-PC has the highest therapeutic index and is the most promising for the treatment of acanthamoebiasis.

Key Words: APC , liposome , keratitis


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