High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures

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dc.contributor.author Rawlinson, Lee-Anne Betty
dc.contributor.author O'Brien, Peter J.
dc.contributor.author Brayden, David James
dc.date.accessioned 2011-07-11T15:32:45Z
dc.date.available 2011-07-11T15:32:45Z
dc.date.copyright 2010 Elsevier B.V. en
dc.date.issued 2010-08
dc.identifier.citation Journal of Controlled Release en
dc.identifier.issn 0168-3659
dc.identifier.uri http://hdl.handle.net/10197/3009
dc.description.abstract Poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is a cationic polymer with potential as an antimicrobial agent and as a non-viral gene delivery vector. The aim was to further elucidate the cytotoxicity of a selected pDMAEMA low molecular weight (MW) polymer against human U937 monocytes and Caco-2 intestinal epithelial cells using a novel multi-parameter high content analysis (HCA) assay and to investigate histological effects on isolated rat intestinal mucosae. Seven parameters of cytotoxicity were measured: nuclear intensity (NI), nuclear area (NA), intracellular calcium ([Ca2+]i), mitochondrial membrane potential (MMP), plasma membrane permeability (PMP), cell number (CN) and phospholipidosis. Histological effects of pDMAEMA on excised rat ileal and colonic mucosae were investigated in Ussing chambers. Following 24-72 hours exposure, 25-50 µg/ml pDMAEMA induced necrosis in U937 cells, while 100-250 µg/ml induced apoptosis in Caco-2. pDMAEMA increased NA and NI and decreased [Ca2+]i, PMP, MMP and CN in U937 cells. In Caco-2, it increased NI and [Ca2+]i, but decreased NA, PMP, MMP and CN. Phospholipidosis was not observed in either cell line. pDMAEMA (10 mg/ml) did not induce any histological damage on rat colonic tissue and only mild damage to ileal tissue following exposure for 60 min. In conclusion, HCA reveals that pDMAEMA induces cytotoxicity in different ways on different cell types at different concentrations. HCA potential for high throughput toxicity screening in drug formulation programmes. en
dc.description.sponsorship Science Foundation Ireland en
dc.format.extent 802304 bytes
dc.format.mimetype application/msword
dc.language.iso en en
dc.publisher Elsevier en
dc.rights All rights reserved.This is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Controlled Release Volume 146, Issue 1, 17 August 2010, Pages 84-92, DOI: 10.1016/j.jconrel.2010.05.002 en
dc.subject High content analysis en
dc.subject Cytotoxicity assays en
dc.subject pDMAEMA en
dc.subject Antimicrobial polymers en
dc.subject Caco-2 intestinal epithelia en
dc.subject.lcsh Polymers in medicine en
dc.subject.lcsh Anti-infective agents en
dc.subject.lcsh Biological assay en
dc.subject.mesh Methacrylates--therapeutic use en
dc.subject.mesh Biological Assay en
dc.subject.mesh Anti-Infective Agents en
dc.title High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.internal.webversions http://dx.doi.org/10.1016/j.jconrel.2010.05.002 en
dc.status Peer reviewed en
dc.identifier.volume 146 en
dc.identifier.issue 1 en
dc.identifier.startpage 84 en
dc.identifier.endpage 92 en
dc.identifier.doi 10.1016/j.jconrel.2010.05.002
dc.neeo.contributor Rawlinson|Lee-Anne Betty|aut| en
dc.neeo.contributor O'Brien|Peter J.|aut| en
dc.neeo.contributor Brayden|David James|aut| en
dc.description.admin au, ke - AL 07/08/2011 en

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