High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures
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|Title:||High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures||Authors:||Rawlinson, Lee-Anne Betty
O'Brien, Peter J.
Brayden, David James
|Permanent link:||http://hdl.handle.net/10197/3009||Date:||Aug-2010||Online since:||2011-07-11T15:32:45Z||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.||Funding Details:||Science Foundation Ireland||Type of material:||Journal Article||Publisher:||Elsevier||Journal:||Journal of Controlled Release||Volume:||146||Issue:||1||Start page:||84||End page:||92||Copyright (published version):||2010 Elsevier B.V.||Keywords:||High content analysis; Cytotoxicity assays; pDMAEMA; Antimicrobial polymers; Caco-2 intestinal epithelia||Subject LCSH:||Polymers in medicine
|DOI:||10.1016/j.jconrel.2010.05.002||Other versions:||http://dx.doi.org/10.1016/j.jconrel.2010.05.002||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Irish Drug Delivery Network Research Collection|
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