Open Access
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
,
SUNIL SHAUNAK
5
,
Joachim H.G Steinke
1
,
Maya Thanou
2
Publication type: Journal Article
Publication date: 2017-04-01
scimago Q1
wos Q1
SJR: 0.988
CiteScore: 10.1
Impact factor: 5.2
ISSN: 03785173, 18733476
PubMed ID:
28232268
Pharmaceutical Science
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.
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199
Total citations:
199
Citations from 2025:
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(14.07%)
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GOST
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Monnery B. D. et al. Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity // International Journal of Pharmaceutics. 2017. Vol. 521. No. 1-2. pp. 249-258.
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Monnery B. D., Wright M., Cavill R., Hoogenboom R., SHAUNAK S., Steinke J. H., Thanou M. Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity // International Journal of Pharmaceutics. 2017. Vol. 521. No. 1-2. pp. 249-258.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1016/j.ijpharm.2017.02.048
UR - https://doi.org/10.1016/j.ijpharm.2017.02.048
TI - Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity
T2 - International Journal of Pharmaceutics
AU - Monnery, Bryn D.
AU - Wright, Michael
AU - Cavill, Rachel
AU - Hoogenboom, Richard
AU - SHAUNAK, SUNIL
AU - Steinke, Joachim H.G
AU - Thanou, Maya
PY - 2017
DA - 2017/04/01
PB - Elsevier
SP - 249-258
IS - 1-2
VL - 521
PMID - 28232268
SN - 0378-5173
SN - 1873-3476
ER -
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BibTex (up to 50 authors)
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@article{2017_Monnery,
author = {Bryn D. Monnery and Michael Wright and Rachel Cavill and Richard Hoogenboom and SUNIL SHAUNAK and Joachim H.G Steinke and Maya Thanou},
title = {Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity},
journal = {International Journal of Pharmaceutics},
year = {2017},
volume = {521},
publisher = {Elsevier},
month = {apr},
url = {https://doi.org/10.1016/j.ijpharm.2017.02.048},
number = {1-2},
pages = {249--258},
doi = {10.1016/j.ijpharm.2017.02.048}
}
Cite this
MLA
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Monnery, Bryn D., et al. “Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity.” International Journal of Pharmaceutics, vol. 521, no. 1-2, Apr. 2017, pp. 249-258. https://doi.org/10.1016/j.ijpharm.2017.02.048.