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Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity

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Abstract

The mechanism of polycation cytotoxicity and the relationship to polymer molecular weight is poorly understood. To gain an insight into this important phenomenon a range of newly synthesised uniform (near monodisperse) linear polyethylenimines, commercially available poly(L-lysine)s and two commonly used PEI -based transfectants (broad 22 kDa linear and 25 kDa branched) were tested for their cytotoxicity against the A549 human lung carcinoma cell line. Cell membrane damage assays (LDH release) and cell viability assays (MTT) showed a strong relationship to dose and polymer molecular weight, and increasing incubation times revealed that even supposedly "non-toxic" low molecular weight polymers still damage cell membranes. The newly proposed mechanism of cell membrane damage is acid catalysed hydrolysis of lipidic phosphoester bonds, which was supported by observations of the hydrolysis of DOPC liposomes. Crown Copyright (C) 2017 Published by Elsevier B.V. All rights reserved.

    Research areas

  • Cytotoxicity, Gene therapy, Hydrolysis, Molecular weight, MTT assay, Phospholipids, SUPPORTED LIPID-BILAYERS, IN-VITRO CYTOTOXICITY, GENE DELIVERY, DNA DELIVERY, LINEAR POLYETHYLENIMINE, CELL VIABILITY, HOLE FORMATION, MEMBRANE, POLYMERS, POLYMERIZATION
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Details

Original languageEnglish
Pages (from-to)249-258
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume521
Issue number1-2
DOIs
Publication statusPublished - 15 Apr 2017