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. 2017 Apr 15;521(1-2):249-258.
doi: 10.1016/j.ijpharm.2017.02.048. Epub 2017 Feb 21.

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

Bryn D Monnery  1 , Michael Wright  2 , Rachel Cavill  3 , Richard Hoogenboom  4 , Sunil Shaunak  5 , Joachim H G Steinke  1 , Maya Thanou  6
Affiliations
Free article

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

Bryn D Monnery et al. Int J Pharm. .
Free article

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 22kDa linear and 25kDa 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.

Keywords: Cytotoxicity; Gene therapy; Hydrolysis; MTT assay; Molecular weight; Phospholipids.

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