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    Determining the effects of PEI adsorption on the permeability of 1,2-dipalmitoylphosphatidylcholine/bis(monoacylglycero)phosphate membranes under osmotic stress

    Year: 2018

    Journal: Acta Biomater., Volume 65, JAN, page 317–326

    Authors: Clark, Scott R.; Lee, Keel Yong; Lee, Hoyoung; Khetan, Jawahar; Kim, Hyun Chang; Choi, Yun Hwa; Shin, Kwanwoo; Won, You-Yeon

    Organizations: National Science Foundation (NSF) [CBET-0828574, DMR-0906567, CBET-1264336]; Global Innovative Research Center (GiRC) Program of the National Research Foundation of Korea: the "Global RNAi Carrier Initiative" Intramural Research Program of the Korea Institute of Science and Technology (KIST) [2012k1A1A2A01056095]; Purdue University Center for Cancer Research (NIH) [P30 CA023168]; NSF [NSF/CHE-1346572]; DOE [DE-AC02-06CH11357]

    Keywords: Polyplex; Polyethylenimine; Adsorption; Gene delivery; Endosomal escape; Proton sponge effect; Cytotoxicity; Antimicrobial property

    Polycations are used for a number of biological applications, including antibiotics and gene therapy. One aspect of the use of polycation gene carriers such as polyethylenemine (PEI) in gene therapy that is not well understood is their ability to escape from the vesicles they are internalized in. Here, in an attempt to gain a better understanding of PEI interaction with endosomal lipids under osmotic stress, we performed investigations using monolayers and vesicles derived from a mixture of neutral and negative lipids (1,2-dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate (BMP), respectively). X-ray reflectivity (XR) and Langmuir trough measurements confirmed PEI adsorption to the negatively charged membrane. Confocal microscopy imaging indicated that PEI adsorption actually increases the overall integrity of the DPPC/BMP vesicle against osmotic stresses while also causing overall deformation and permeabilization of the lipid membrane, thus leading to leakage of contents from the interior of the vesicle. These confocal microscopy observations were also supported by data gathered by dynamic light scattering (DLS). (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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