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  The effect of molar mass and degree of hydroxyethylation on the controlled shielding and deshielding of hydroxyethyl starch-coated polyplexes

Noga, M., Edinger, D., Kläger, R., Wegner, S., Spatz, J. P., Wagner, E., et al. (2013). The effect of molar mass and degree of hydroxyethylation on the controlled shielding and deshielding of hydroxyethyl starch-coated polyplexes. Biomaterials, 34(10), 2530-2538. doi:10.1016/j.biomaterials.2012.12.025.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-768C-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-7721-C
Genre: Journal Article

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Biomaterials_34_2013_2530.pdf (Any fulltext), 937KB
 
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 Creators:
Noga, Matthäus, Author
Edinger, Daniel, Author
Kläger, Raphaela, Author
Wegner, Seraphine1, 2, Author              
Spatz, Joachim P.1, 2, Author              
Wagner, Ernst, Author
Winter, Gerhard, Author
Besheer, Ahmed, Author
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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Free keywords: Hydroxyethyl starch (HES); Linear polyethylenimine (LPEI); Gene delivery; Biodegradable coating; Amylase; Quartz-crystal microbalance (QCM-D)
 Abstract: PEGylation is currently the gold-standard in shielding cationic DNA-polyplexes against non-specific interaction with blood components. However, it reduces cellular uptake and transfection, in what is known as the "PEG-dilemma". In an approach to solve this problem we developed hydroxyethyl starch (HES)-shielded polyplexes which get deshielded under the action of alpha amylase (AA). In this study, the effect of molar mass and degree of hydroxyethylation on the shielding and deshielding of the polyplexes as well as their in vivo performance were investigated. For this purpose, a battery of HES-polyethylenimine (PEI) conjugates was synthesized, and their rate and extent of biodegradation were investigated using asymmetric flow-field flow fractionation (AF4) and quartz-crystal microbalance with dissipation (QCM-D). Additionally, the transfection efficiency of the polyplexes was tested in Neuro2A cells and tumor-bearing mice. AF4 and QCM results show a rapid degradation for HES with lower degrees of hydroxyethylation. Meanwhile, in vitro transfection experiments showed a better shielding for higher HES molar masses, as well as deshielding with a significant boost in transfection upon addition of AA. Finally, in vivo experiments showed that the biodegradable HES markedly reduced the non-specific lung transcription of the polyplexes, but maintained gene expression in the tumor, contrary to the non-degradable HES and PEG controls, which reduced both tumor and lung expression. This study shows that by controlling the molecular characteristics of HES it is possible to engineer the shielding and deshielding properties of the polyplexes for more efficient gene delivery.

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Language(s): eng - English
 Dates: 2012-10-272012-12-222013-01-112013-03-01
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Biomaterials
Source Genre: Journal
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Publ. Info: Guildford, England : Elsevier
Pages: - Volume / Issue: 34 (10) Sequence Number: - Start / End Page: 2530 - 2538 Identifier: ISSN: 0142-9612
CoNE: https://pure.mpg.de/cone/journals/resource/954925472369